HX641 02769 
QP111  .H81  On  the  escape  of  the 


RECAP 


DEPARTMEliT  OF  PHYSm 


487  WEST  RPry-NIMTH  a 
NEW  YORK 


ON  THE  ESCAPE  OE  THE  HEART 
EROM  VAGUS  INHIBITION. 


^   SljestB 


PRESENTED  TO  THE  BOARD  OE  UNIVERSITY  STUDIES  OF 

THE  JOHNS  HOPKINS  UNIVERSITY  FOR  THE  DEGREE 

OF  DOCTOR  OF  PHILOSOPHY. 


BY 


THEODORE  HOUGH. 


REPRINTED    FROM 
THE    JOUKXAL    OF    PHYSIOLOGY,    VOL.    XVIII. 

1895. 


Columbia  (Mnitierfiftti) 

intljeCitpofBfttigtJrk 

€oQege  of  $f)p£itcian£e  anb  burgeons: 
Hibrarp 


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ON  THE  ESCAPE  OF  THE  HEART 
EROM  VAGUS  INHIBITION. 


3.    ®licsi0 


PRESENTED  TO  THE  BOARD  OF  UNIVERSITY  STUDIES  OF 

THE  JOHNS  HOPKINS  UNIVERSITY  FOR  THE  DEGREE 

OF  DOCTOR  OF  PHILOSOPHY. 


BY 

THEODOKE  HOUGH. 


REPRINTED    FROM 
THE    JOUPvXAL    OF    PHYSIOLOGY,    VOL.    XVIII. 

18  95. 


QPHI 
H8/ 


[Fro7n  the  Journal  of  Physiology.      Vol.  XVIII.  No.  3,   1895.] 


ON  THE  ESCAPE  OF  THE  HEART  FROM  VAGUS 
INHIBITION.  By  THEODORE  HOUGH,  Ph.D.  (Four 
Figures  in  Text.) 

{From  the  Biological  Laboratory,  Johns  Hopkins  University 
of  Baltimore,   U.  S.  A.) 

Contents. 

Section  1.  Introductory.  The  escape  of  the  heart  from  vagus  in- 
hibition is  not  the  result  of  exhaustion  of  the  fibres  of  the  vagus 
nerve. 

Section  2.  The  efficiency  of  inhibition  varies  inversely  with  the  vigour 
of  the  heart. 

Section  3.  Technique  of  experiments.  Description  of  the  typical 
curves  of  escape  for  the  terrapin,  dog,  rabbit,  and  cat. 

Section  4.  The  heart  escapes,  no  matter  how  slight  the  initial 
slowing. 

Section  5.  Rapidity  of  recovery  by  the  inhibitory  mechanism  of  the 
power  to  produce  stand-still. 

Section  6.  Relation  between  the  strength  of  stimulus  and  the  curve 
of  escape. 

Section  7.     On  alternate  stimulation  of  the  vagi. 

Section  8.     Summary. 

1.  Introductory.  The  Escape  of  the  Heart  from  Vagus 
Inhibition  is  not  the  Result  of  the  Exhaustion  of  the 
Fibres  of  the  Vagus  Nerve. 

Why  does  stimulation  of  the  vagus  nerve  fail  to  keep  the  heart  of  a 
mammal  at  stand-still  ?  This  question  has  been  frequently  asked  and 
has  received  various  answers.  It  was  formerly  supposed  that  the  fibres 
of  the  vagus  are  in  some  respect  different  from  other  nerve  fibres  in 
that  they  are  more  easily  exhausted  by  stimulation;  this  exhaustion 
has,  moreover,  been  attributed  either  to  the  continued  conduction  of 
nervous  impulses  to  the  end  organ  or  to  a  loss  of  irritability  at  the 

PH.  XVIII.  11 


162  T.   HOUGH. 

point  of  stimulation.  The  work  of  Wedenski,  Bowditch,  and  others 
has,  however,  rendered  very  improbable  the  possibility  of  rapid  ex- 
haustion of  a  medullated  nerve  fibre,  and  the  following  experiment 
shows  that  this  is  not  the  explanation  of  the  phenomenon  under  dis- 
cussion :  five  or  more  centimetres  of  the  cervical  vagus  are  prepared 
and  the  peripheral  portion  laid  in  a  metal  trough,  which  can  be  cooled 
by  a  stream  of  water -flowing  around  it;  having  determined  the 
efficiency  of  inhibition,  the  peripheral  portion  of  the  nerve  is  cooled  to 
the  neighbourhood  of  0°C.,  by  which  it  is  rendered  non-conductive;  the 
nerve  is  then  stimulated  centrally  of  this  point  for  five  or  ten  minutes ; 
on  warming  the  cooled  portion  of  the  nerve  (by  replacing  the  stream  of 
cold  water  with  one  of  warm  water)  it  is  found  that  the  heart  is  brought 
to  rest  and  remains  inhibited  as  long  as  during  the  previous  stimu- 
lation. 

Here  the  nerve  was  evidently  stimulated  a  much  longer  time  than 
is  ever  required  in  the  dog  for  the  appearance  of  escape ;  it  could  not 
have  been  injured  appreciably  at  the  point  of  stimulation,  and  the 
conduction  of  impulses  from  this  point  to  the  cooled  j)ortion  (over  an 
inch  intervened  between  the  electrodes  and  the  trough)  could  not  have 
produced  any  exhaustion.  In  other  wordsj  so  long  as  the  inhibitory 
fibres  remain  fine  medullated  fibres  of  the  vagus  nerve  they  can  be 
tired  out  neither  by  stimulation  nor  by  conduction. 

2.    The  Efb^iciency  of  Inhibition  varies  inversely  with  the 
Vigour  of  the  Heart, 

It  is  frequently  stated  that  the  more  vigorous  the  heart  the  easier 
it  is  to  bring  about  inhibition,  and  this  seems  to  have  been  believed 
ever  since  the  inhibitory  action  of  the  vagus  was  known.  One  reads, 
for  example,  in  one  of  the  best  text-books  of  physiology  in  the  English 
language :  "  When  the  nerve  and  the  heart  are  in  good  condition,  it 
needs  only  a  slight  stimulus,  a  weak  current  to  produce  a  marked 
effect,  and  it  may  he  mentioned  that  the  more  vigorous  the  heart,  the  more 
rapidly  it  is  heating,  the  easier  it  is  to  hring  uhout  inhihition." 

I  am  not  aware  of  the  experiments  upon  which  this  statement  is 
based,  nor  do  I  forget  that  it  is  made  with  reference  to  an  animal  (frog) 
upon  which  I  have  not  worked,  and  whose  cardiac  vagus  is  peculiar  in 
containing  accelerator  fibres.  I  am  sure,  however,  that  in  the  cat  and 
the  dog  the  more  vigorous  the  heart,  as  shown  by  the  pulse  and  blood- 
pressure,  the  more  difficult  it  is  to  cause  inhibition. 


ESCAPE  FROM  VAGUS  INHIBITION.  163 

The  comparative  efficiency  of  vagus  inhibition  in  strong  and  weak 
hearts  respectively  may  be  measured  in  several  ways :  (1)  by  the  extent 
of  slowing  produced ;  (2)  by  the  length  of  time  the  heart,  if  stopped,  is 
held  at  stand-still ;  (3)  by  the  rapidity  or  extent  or  both  of  escape 
during  prolonged  stimulation. 

Whatever  method  be  used  we  may  either  compare  two  animals,  one 
of  which  apparently  has  a  weaker  heart  than  the  other,  or  we  may 
compare  during  the  course  of  the  same  experiment  the  same  heart 
under  different  conditions.  It  is  seldom  possible  to  keep  an  animal  for 
two  or  three  hours  after  the  operation  in  exactly  the  same  condition  as 
regards  rate  of  beat  and  pressure ;  it  generally  happens,  especially  in 
the  case  of  cats,  that  there  is  a  gradual  weakening  of  the  heart ;  the 
pulse  will  fall  from  180 — 200  per  minute  to  120 — 140,  and  this  will  be 
accompanied  by  a  fall  of  blood-pressure.  It  is  fair,  I  think,  to  suppose 
that  such  a  heart  is  not  so  vigorous  at  the  end  of  the  experiment  as  it 
was  at  the  beginning.  On  the  other  hand  it  sometimes  happens  that 
the  heart  becomes  more  vigorous  as  the  experiment  progresses ;  the 
morphia,  for  instance,  given  to  a  dog  as  an  anaesthetic  may  be  an 
overdose ;  so  that  at  first  {i.e.  some  two  hours  after  the  injection)  the 
heart  is  beating  feebly  and  slowly;  gradually  toward  the  end  of  the 
experiment  (one  to  two  hours  later)  as  the  morphia  is  excreted  a  gradual 
improvement  is  noticed  in  the  pulse. 

It  should,  perhaps,  be  said  that  I  have  not  specially  investigated 
the  question  which  is  under  discussion  in  this  section  of  my  paper ;  at 
the  same  time  I  think  it  can  be  shown  that  the  numerous  experiments 
with  different  strengths  of  current  and  upon  animals  in  different  con- 
ditions of  nutrition,  although  made  with  other  objects  in  view,  afford 
unquestionable  evidence  on  this  point. 

First,  then,  as  to  the  extent  of  slowing  with  the  same  strength  of 
stimulation  in  vigorous  and  weakened  hearts  respectively.  Perhaps  the 
best  evidence  of  this  kind  is  afforded  by  experiments  upon  cats.  In  a 
strong,  healthy  cat  with  the  normal  blood-pressure  (120 — 180  mm.  of 
mercury)  and  pulse  (27 — 32  beats  per  ten  seconds)  it  is  almost,  if  not 
quite  impossible  to  stop  the  heart  by  stimulation  of  one  or  both  vagi 
with  any  strength  of  current  whatever.  I  had  made  some  twenty 
experiments  on  cats  before  a  single  case  of  stand-still  occurred ;  usually 
upon  stimulation  blood-pressure  falls  for  one  or  two  seconds,  but  before 
complete  diastole  has  occurred  the  beats  recommence  and  the  escape  of 
the  heart  is  comparatively  rapid.  For  a  full  account  of  the  conduct  of 
the  cat's  heart  during  prolonged  stimulation  see  page  183. 

11—2 


1G4 


T.   HOUGH. 


This  is  what  always  happens,  unless  for  some  reason  or  other  the 
heart  has  been  weakened ;  when,  however,  as  the  result  of  too  much 
ether,  chloral,  or  paraldehyde,  or  from  any  other  cause  the  pulse  is  slow 
and  more  or  less  feeble,  stimulation  of  the  vagi  is  much  more  effective ; 
the  slowing  of  the  heart  and  the  fall  of  blood-pressure  are  more  pro- 
nounced, the  rate  remains  at  a  lower  level ;  and  in  some  cases  quite 
prolonged  stand-still  is  produced.  This  result  is  so  constant,  there  not 
being  in  all  my  work  a  single  exception  to  it,  that  I  have  given  it  as 
the  first  reason  for  believing  that  the  weaker  the  heart,  the  more  feebly 
it  is  beating,  the  more  effective  is  vagus  stimulation. 

Experiments  41  and  46  may  be  cited  as  cases  in  point. 

In  experiment  41,  2^  grammes  of  paraldehyde  dissolved  in  GOc.c.  of 
water  were  injected  into  the  stomach ;  this  was  not  quite  sufficient  to 
produce  unconsciousness,  so  that  a  little  ether  was  added ;  both  vagi 
were  cut  and  one  or  the  other  stimulated.  As  frequently  happens  with 
the  cat,  moderately  strong  stimulation  with  its  resulting  systemic 
changes  brought  about  a  loss  of  irritability  of  the  cord  and  medulla,  so 
that  the  animal  ceased  breathing  and  artificial  respitation  had  to  be 
used  ;  by  this  means  the  animal  was  kept  alive  for  more  than  an  hour; 
both  the  rate  of  beat  and  the  blood-pressure,  however,  remained  low, 
indicating  an  enfeebled  condition  of  the  heart.  Stimulation  of  one 
vagus  under  these  conditions  with  strong  or  moderately  strong  currents 
was  quite  effective,  as  the  following  figures  show ;  the  pulse  and  pres- 
sure are  given  for  each  ten  seconds.  These  figures  should  be  compared 
with  the  results  obtained  on  cats  whose  hearts  were  beating  with 
normal  force  and  frequency. 


No. 

hrs. 

Time 
min. 

sees 

II 

3 

44 

20 
30 

40 

3 

45 

30 
40 

III 

3 

50 

20 
30 
40 

3 

51 

30 
40 

Fractions 
in  sees. 

Eate 

Pressure 

19 

61 

5 

11 

49 

5 

35 

10 

31 

15 

44 

18 

45 

18 

62 

7 

30 

15 

46 

22 

68 

22 

69 

Remarks 


Lat  10 


Off 


R  at  5 


Off 


ESCAPE  FROM   VAGUS  INHIBITION. 


165 


Time 

No. 

hrs. 

min. 

sees 

IV 

3 

56 

10 
20 

30 

3 

57 

40 
50 

X 

4 

42 

40 
50 

4 

53 

4 

55 

20 
30 
40 

Fractions 
in  sees. 

Bate 

Pressure 

19 

89 

5 

8 

63 

5 

50 

9 

43 

15 

58 

18 

62 

20 

82 

6 

42 

6 

50 

16 

59 

16 

63 

20 

69 

Kemarks 


R  at  10 

Off 
R  at  6 

Off 


The  results  of  most  experiments  are  given  in  this  form  ;  the  first  column 
gives  the  number  of  the  tracing  in  the  experiment;  the  second,  the  time; 
the  fourth,  the  pulse  ;  and  the  fifth,  the  pressure.  The  time  is  given  in  periods 
of  ten  seconds  ;  if  for  any  reason  it  is  advisable  to  give  the  rate  and  pressure 
for  shorter  periods  of  time  this  is  indicated  by  the  third  column,  which  gives 
the  fractions  (in  seconds)  of  that  ten  seconds.  Thus  in  the  second  tracing  of 
the  above  experiment  the  figures  indicate  that  between  3hrs.  44mins.  30secs. 
and  3hrs.  44mins.  40secs.  the  heart  gave  eleven  beats ;  that  during  the  first 
five  seconds  of  this  period  the  average  blood-pressure  was  49mm.  of  mercury, 
and  during  the  second  five  seconds  35  mm.  of  mercury. 

In  subsequent  protocols  it  is  to  be  understood  that  the  period  of  stimula- 
tion is  indicated  in  the  last  column,  and  that  the  stimulation  is  continued 
until  some  change  is  indicated  in  the  same  column.  Thus  3.45.20,  L  at  6 
means  that  at  45mins.  20secs.  past  three  o'clock  the  left  nerve  was  stimulated 
with  the  secondary  coil  of  the  induction  appai-atus  6  cm.  from  the  primary 
coil.  R  means  that  the  right  nerve  is  stimulated ;  B  that  both  are  simul- 
taneously stimulated.     Cessation  of  stimulation  is  indicated  by  "Off." 

Tracings  5,  6,  7,  8,  and  9  of  the  above  experiment  give  similar 
results  to  those  shown  in  the  table.  In  all  cases  the  amount  of  slowing 
is  much  greater  than  occurs  ordinarily  in  vigorous  animals. 

In  experiment  46  a  small  cat  was  kept  under  the  influence  of  ether 
during  the  operation,  which  the  animal  did  not  stand  well ;  so  that, 
although  after  the  operation  no  ether  was  administered,  not  even  the 
lid  reflex  was  present.  Artificial  respiration.  The  pulse  gradually  sank 
from  21  to  14  beats  per  ten  seconds,  while  the  pressure  at  all  times 
(largely  due  to  failure  of  the  vaso-motor  centre  to  maintain  the  tone  of 
the  small  arteries)  was  very  low.     More  unfavourable  conditions  could 


166 


T.   HOUGH. 


not  well  be  desired;    and  the  following  figures  will  show  that  vagus 
stimulation  was  able  in  all  cases  to  stop  the  heart. 


No. 


VII 


Time 

Fractions 

Rate 

rs. 

min. 

sees. 

in  sees. 

3 

24 

10 
20 
30 
40 

21 
0 
0 

14 

3 

26 

10 
20 

17+ 

18 

19 

4 

23 

10 
20 

14 
0 
0 

30 

3 

7 

0 
2 

40 

*3+ 

4 

28 

20 
30 
40 

8 

9 

12 

Pressure 


Bemarks 


3.24.20  R  at  8 


3.26.10  Off 


4.23.10  R  at  8 


4.28.30  Off 


*  .3  +  means  that  between  3  and  3^  beats  were  given ;  4  -  between  3^  and  4  beats ;  a 
beat  being  measured  between  any  two  corresponding  points  of  the  cardiogram. 

Tracings  4,  5,  and  6  gave  similar  results. 

For  convenience  of  reference  I  insert  the  results  of  a  typical  tracing 
taken  from  a  vigorous  cat. 


Exp.  22.     Ether ;  both  vagi  cut  and  stimulated. 

Time 


No. 

hrs. 

min. 

sees 

Ill 

3 

25 

20 
30 
40 
50 

3 

28 

10 

Fractions 
in  sees. 

Bate 

Pressure 

28 

154 

9 

80 

12 

82 

17 

93 

23 

126 

Bemarks 


3.25.30  Bat6i 


In  what  has  just  been  said  the  efficiency  of  vagus  stimulation  in 
strong  animals  has  been  compared  with  that  in  weak  ones,  and  it  is 
evident  that  it  is  possible  to  greatly  slow  or  even  stop  the  heart  of  a 
weak  animal  by  the  use  of  a  stimulus  which  in  a  vigorous  animal  is 
unable  to  do  more  than  cause  a  comparatively  slight  and  transient 
slowing  followed  by  a  rapid  and  almost  immediate  escape. 

We  now  pass  to  a  comparison  of  tracings  taken  from  the  same 
animal  under  different  physiological  conditions  but  during  the  same 
experiment.     It  should  be  remembered  at  the  outset  that  the  unavoid- 


ESCAPE  FROM   VAGUS  INHIBITION. 


167 


able  presence  of  secondary  factors  or  of  slight  experimental  errors  may 
at  any  time  obscure  the  effect  of  the  condition  of  the  heart ;  such 
secondary  factors  are  variations  in  the  contact  of  the  nerve  with  the 
electrodes,  or  of  the  strength  of  current  in  the  primary  circuit,  or  of  the 
condition  of  the  nerve  itself;  consequently  we  are  not  justified  in 
comparing  tracings,  differences  of  which  in  rate  and  pressure  are 
comparatively  slight  (say  5 — 20  beats  per  minute) ;  it  is  only  when  the 
difference  is  considerable  that  we  can  expect  the  effect  of  the  condition 
of  the  heart  always  to  be  apparent  in  the  graphic  record.  Such  com- 
parisons leave  no  room  for  doubt. 

Let  us  consider  those  experiments  where  a  heart  at  first  strong  and 
vigorous  became  either  suddenly  or  gradually  weaker  while  under 
observation.  During  experiment  24  the  first  tracing  gave. the  following 
result : 


No. 

I 


hrs. 
3 


Time 


50 


51 


10 
20 
30 
40 
20 


Fractions 
in  sees. 

Eate 

Pressure 

29 

98 

9 

50 

14 

56 

78 

23 

80 

22 

80 

Eemarks 


3.50.10  L  at  8 


Shortly  after  taking  this  tracing  the  cat  went  too  deeply  under  the 
influence  of  ether  and  could  be  kept  alive  only  by  the  use  of  artificial 
respiration ;  blood-pressure  during  the  rest  of  the  experiment  was  very 
low  (50 — 60  mm.  of  mercury).  It  was  then  found  that  in  the  three 
subsequent  tracings  the  strength  of  stimulus  used  above  stopped  the 
heart.  This  is  a  striking  instance  of  the  influence  of  the  condition  of 
the  heart  upon  its  sensitiveness  to  inhibition  ;  the  difference  in  vitality 
is  very  marked,  and  stimulation  of  the  vagus  shows  a  most  marked 
increase  in  efiiciency  as  the  heart  beats  less  vigorously. 

Experiment  44  is  even  more  striking ;  this  cat  gave  three  approxi- 
mately normal  tracings ;  after  the  third  the  irritability  of  the  vaso- 
motor and  respiratory  centres  was  more  or  less  impaired.  Artificial 
respiration.  Tracings  5  and  6  taken  from  this  period  show  that  the 
rate  and  blood-pressure  had  been  lowered,  and  the  slowing  is  much 
more  pronounced  with  the  same  stimulus.  After  taking  the  seventh 
tracing  too  much  ether  was  given,  and  there  was  a  still  further  fall  of 
pulse  rate  and  pressure,  both  of  which  were  now  at  a  very  low  level 
(98  beats  per  minute  and  57  mm.  Hg.  respectively);  stimulation  with 


168 


T.   HOUGH. 


the  weaker  of  the  two  currents  previously  used  now  caused  complete 
stand-still,  which  lasted  for  52  sees.,  and  it  was  not  \mtil  the  expiration 
of  six  minutes  that  the  heart  was  able  to  give  even  three  beats  in  ten 
seconds. 

Besides  such  cases  of  sudden  collapse  there  are  others  where  during 
a  long  experiment  the  heart-beats  steadily  decline  in  rate  and  force. 
No  matter  how  gi-adual  this  decline  may  be,  1  have  not  seen  a  single 
case  where  the  efficiency  of  inhibition  did  not  correspondingly  increase. 
A  striking  example  of  it  is  found  in  experiment  29,  which  is  given  ;  at 
least  six  others  show  the  same  thing. 


No. 
II 


III 


IV 


VII 


Time 

hrs.    min.    sees. 

3       55       20 

30 

40 

50 


57 


11 
12 

18 


26 


54 


56 


10 

10 
20 
30 
40 
20 
30 
40 

40 
50 

10 

20 

10 

30 

40 
50 

10 
20 

10 
20 
30 
40 
50 
40 
50 


Fractions 
in  sees. 

Rate 

Pressure 

38 

180 

13 

108 

12 

114 

21 

135 

25 

156 

35 

178 

15 

120 

14 

120 

22 

155 

24 

162 

25 

166 

31 

176 

32 

168 

13 

104 

12 

106' 

18 

120 

20 

128 

17 

102 

32 

163 

10 

87 

10 

90 

18 

96 

22 

138 

22 

132 

5 

58 

6 

53 

10 

66 

11 

70 

12 

72 

13 

92 

Bemarks 
3.55.30   B  at  6^ 

3.57.10    Off 
4.*3.20   B  at  6 

4.8.30   Off 
4.11.50   Bat  7 

4.18.10   Off 
4.25.40   B  at  6 

4.26.20   Off 
4.54.10   B  at  6 


4.56,50   Off 


ESCAPE  FROM   VAGUS  INHIBITION. 


169 


As  already  said,  it  occasionally  happens  that  the  beat  of  the  heart 
improves  as  an  experiment  progresses ;  the  shock  of  the  operation  or 
some  other  cause  may  for  a  time  exercise  an  injurious  influence  which 
gradually  wears  off,  so  that  the  heart  comes  to  beat  more  rapidly  and 
blood-pressure  rises.  In  some  of  these  cases  the  experimental  procedure 
was  such  that  the  efficiency  of  inhibition  could  be  compared  in  different 
tracings,  and  this  was  found  to  diminish  as  the  condition  of  the  heart 
improved.     Two  such  experiments  are  30  and  48,  both  on  dogs. 

In  the  former  the  rate  increased  from  20  to  25  or  26  beats  per  ten 
seconds.  The  rise  of  blood-pressure  was  even  more  marked.  At  first 
the  heart  could  be  brought  to  rest  with  the  secondary  coil  at  13  cm. 
After  the  improvement  in  its  rate  and  force  of  beat  stand-still  could 
not  be  produced  with  the  secondary  coil  more  than  7;|cm.  from  the 
primary. 

Experiment  48  was  upon  a  young  dog,  and  is  noteworthy  since  (in 
consequence  of  the  age  of  the  animal  ?)  it  was  almost  impossible  to  stop 
the  heart.  Tracings  6  and  10  were  each  taken  with  the  secondary  coil 
at  6  cm.  from  the  primary. 


Eemarks 


3.34.20   R  at  6 


Time 

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Fractions 
in  sees. 

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Pressure 

27 

115 

n 

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130 

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Of  course  it  may  be  objected  to  these  results  that  what  has  been 
attributed  to  diminished  efficiency  of  inhibition  is  only  the  result  of  the 
loss  of  a  certain  amount  of  irritability  in  the  nerve  consequent  upon 
exposure  or  other  insult;  without  denying  that  this  factor  plays  some 
part,  it  must  be  remembered  that  the  necessity  of  increasing  the 
stimulus  to  produce  the  same  effect  occurred  in  every  experiment  of 


170  T.   HOUGH. 

the  kind  whose  tracings  can  be  compared  ;  and,  I  may  add,  never  was 
it  found  necessary  to  do  this  in  the  many  cases  where  the  opposite 
change  of  condition  occurred. 

We  may  also  measure  the  efficiency  of  inhibition  by  the  duration  of 
the  initial  slowing  or  stand-still ;  other  things  being  equal  we  should 
certainly  consider  that  inhibition  the  more  effective  which  is  able  to 
maintain  itself  the  longer  time. 

We  have  seen  that  in  the  vigorous  heart  of  a  cat  escape  is  almost 
immediate,  no  matter  what  strength  of  current  be  used,  and,  as  a 
general  thing,  by  the  end  of  twenty  seconds  after  stimulation  the  heart 
is  beating  very  much  more  rapidly  than  it  did  during  the  first  three 
seconds.  This  curve  of  escape  for  the  cat  is  very  constant  and  charac- 
teristic. Reference  to  the  tracings  of  the  hearts  of  weak  cats  that  have 
already  been  given  will  show  that  for  twenty  seconds  or  more  there  is 
little  or  no  escape ;  this  delay  in  the  appearance  of  escape  is  as  charac- 
teristic in  these  hearts  with  less  rapid  beat  and  lower  pressure  as  is  the 
early  appearance  of  the  same  in  strong  hearts. 

In  the  dog,  on  the  other  hand,  it  is  almost  always  possible  to  bring 
the  heart  to  rest  for  twenty  seconds  or  more,  although  the  strength  of 
current  required  to  do  this  varies  in  different  individuals ;  so  that  we 
may  consider  the  duration  of  stand-still  as  affording  a  measure  of  the 
efficiency  of  inhibition.  In  doing  so,  however,  the  same  caution  applies 
which  has  already  been  given  in  the  discussion  of  a  similar  case ;  we 
should  choose  for  comparison  only  hearts  which  are  in  decidedly 
different  conditions,  so  that  we  may  be  the  more  assured  that  the 
differences  in  the  duration  of  stand-still  are  to  be  traced  back,  partially 
at  least,  to  the  condition  of  the  heart,  and  are  not  the  result  of  other 
factors. 

It  is  indeed  found  that  if  only  those  cases  are  considered  which 
differ  but  slightly  from  one  another  the  relation  in  question  does  not 
appear  at  all ;  but  if  we  compare  tracings  which  show  decided  differ- 
ences the  following  is  found  to  be  true :  long  stand-stills  are  the  rule  in 
weak  hearts,  comparatively  rare  in  strong,  and  especially  so  in  young 
ones;  moreover  instances  of  slight  efficiency  of  vagus  stimulation  occur 
only  in  vigorous  hearts. 

Beginning  with  the  last  statement  I  find  that  only  in  experiments 
3,  9,  and  48  was  vagus  stimulation  unable  to  cause  stand-still  in  the 
dog.  In  all  these  cases  while  there  was  not  a  remarkably  high  blood- 
pressure  nor  rapid  pulse  there  was  throughout  the  whole  experiment  a 
thoroughly  normal   pressure    and    rhythm  ;   nor  is  the  presence   of  a 


ESCAPE  FROM   VAGUS  INHIBITION.  171 

supra-normal  rate  and  pressure  a  fair  test  of  an  exceptionally  vigorous 
heart,  especially  when  they  are  considerably  above  the  normal ;  a  rapid 
rate  may  result  from  accelerator  influence  and  a  high  pressure  from 
over-constriction  of  the  systemic  arterioles,  either  of  which  throws  extra 
work  upon  the  heart  and  so  must  more  or  less  weaken  it ;  the  main- 
tenance throughout  a  long  experiment  of  a  steady  rate  of  22 — 25  beats 
per  ten  seconds  and  of  a  blood-pressure  of  116 — 130  mm.  of  mercury  is, 
it  seems  to  me,  a  good  sign  of  a  vigorous  heart ;  and  this  was  present 
noticeably  in  experiments  3  and  9 ;  in  experiment  48  the  rate  was 
somewhat  higher,  26 — 28  beats  per  ten  seconds — probably  connected 
with  the  fact  that  it  was  a  young  animal. 

It  is  thus  seen  that  every  case  where  stand-still  could  not  be 
produced  gave  indications  of  a  healthy,  vigorous  heart ;  this  is  not  the 
same  thing  as  saying  that  vigorous  hearts  are  always  hard  to  inhibit, 
for  some  long  stand-stills  occur  with  such  hearts ;  unquestionably  there 
are  other  factors  than  the  nutritional  condition  of  the  organ  at  work  to 
which  we  must  look  for  the  complete  explanation  of  the  results ;  the 
important  point  is  that  the  failure  to  inhibit  occurs  only  in  vigorous 
hearts,  while  weak  ones  can  always  be  brought  to  a  comparatively  long 
rest. 

Before  leaving  this  part  of  the  subject  I  should,  perhaps,  mention 
an  interesting  fact  which  becomes  more  or  less  intelligible  if  weaker 
hearts  give  longer  stand-stills ;  in  dogs  the  initial  stand-still  is  almost 
always  of  much  shorter  duration  than  any  subsequent  one ;  it  is  as  if 
the  stoppage  of  the  heart  with  the  concomitant  respiratory  and  other 
changes  exercises  an  injurious  action  upon  the  organ,  so  that,  so, 
to  speak,  it  is  unable  to  escape  so  easily  from  inhibitory  influences. 

Little  need  be  said  of  the  relation  of  the  condition  of  the  heart  to 
the  curve  of  escape,  since  such  curves  are  not  easily  compared  with  one 
another ;  there  is,  however,  one  point  which  should  be  mentioned ; 
when  during  the  course  of  two  hours  the  vagus  nerve  has  been 
stimulated  six  or  eight  times,  for  ten  minutes  more  or  less  each  time,  it 
frequently  happens  that  the  heart  seems  unable  to  escape  successfully 
from  inhibition ;  at  first  there  is  what  promises  to  become  the  regular 
curve  of  escape ;  i.e.  the  heart  is  gradually  gaining  in  frequency  and 
force  of  beat ;  or,  having  ceased  to  do  this,  is  pulsating  with  a  regular 
and  even  rhythm ;  suddenly  the  beats  become  more  infrequent,  finally 
perhaps  ceasing  altogether  for  ten  or  more  seconds;  after  this  escape 
occurs  again,  and  this  escape  may  be  followed  by  another  period  of 
total  inhibition ;  in  such  cases  blood-pressure  rises  only  slightly  during 


172  T.  HOUGH. 

escape,  and  the  impression  is  made,  when  one  examines  such  curves, 
that  the  mechanism  of  the  heart-beat  cannot  maintain  itself  against 
the  inhibitory  impulses.  These  curves  will  be  described  more  in  detail 
in  another  part  of  this  paper;  whatever  may  be  their  true  explanation 
they  indicate  great  efficiency  of  the  inhibitory  impulses,  and  occur 
only  toward  the  end  of  a  long  experiment,  when  the  heart  is  presumably 
weaker  than  it  was  at  first,  or  else  with  the  use  of  very  strong  stimuli. 
The  conditions  of  their  appearance  afford  very  strong  evidence  that  a 
weak  heart  is  more  easily  inhibited  than  a  strong  one. 

To  recapitulate  the  arguments  adduced  in  the  above  discussion : — 
1.  In  the  vigorous  heart  of  the  cat  no  strength  of  stimulation  can 
cause  great  slowing,  while  in  a  heart  which  has  been  appreciably 
weakened  the  slowing  produced  is  always  decided,  and  frequently 
amounts  to  stand-still.  2.  When  the  heart  of  the  same  animal 
becomes  gradually  or  suddenly  weaker  in  the  course  of  an  experiment 
a  decided  increase  in  inhibitory  efficiency  is  noticed ;  conversely,  when 
the  heart  becomes  stronger  during  the  same  experiment,  strengths  of 
stimulation  which  at  first  were  able  to  cause  stand-^till  are  no  longer 
able  to  do  so.  3.  Other  things  being  equal,  the  duration  of  stand-still 
or  of  a  certain  amount  of  inhibition  is  greater  in  weak  hearts  than  in 
strong  ones.  4.  The  heart  of  a  dog  or  a  cat,  weakened  by  repeated 
inhibitions,  very  frequently  toward  the  end  of  the  experiment  shows 
itself  unable  to  escape  effectively  to  a  regular  rate  and  force  of  beat. 

3.  Technique  of  Experiments.  Description  of  the  typical 
Curves  of  Escape  for  the  Terrapin,  the  Dog,  the  Rabbit, 
and  the  Cat. 

It  may  be  well  before  going  farther  to  attempt  a  general  description 
of  the  curves  of  escape,  or,  what  amounts  to  the  same  thing,  the  effects 
of  prolonged  stimulation  of  the  vagus  upon  the  blood-pressure  curve,  as 
studied  in  different  animals. 

My  experiments  were  made  upon  four  animals;  the  terrapin,  the 
dog,  the  rabbit,  and  the  cat ;  and  one  object  of  this  section  of  my  paper 
is  to  emphasize  the  differences  in  the  conduct  of  these  animals  under 
prolonged  stimulation.  Meyer^  showed  that  in  cold-blooded  animals,  in 
general,  vagus  inhibition  is  more  effective  than  it  is  in  warm-blooded 
animals.  In  snakes  he  was  able  to  hold  the  heart  at  stand-still  for 
half-an-hour  or  more ;  and  in  one  experiment  on  Clemmys  decussata 

'  A.B.Meyer.     Das  Hemmungsnervensystem  dcs  Herzens.     Berlin,  1869. 


ESCAPE  FROM   VAGUS  INHIBITION.  173 

(Bell),  a  large  turtle  from  the  Antilles,  he  was  able  by  stimulation  of 
both  vagi  together  to  bring  about  uninterrupted  stand-still  for  an  hour ; 
on  ceasing  the  stimulation  the  heart  again  began  to  pulsate.  In  other 
experiments  on  terrapins  and  turtles  he  notes  spontaneous  beats  as 
occurring  after  a  stand-still  of  ten  or  more  minutes. 

I  have  made  experiments  upon  Pseudemys  mgosa,  and  one  experi- 
ment on  a  species  of  Ghrysemys.  From  Meyer's  account  one  is  led  to 
think  that  these  long  stoppages  unbroken  by  any  spontaneous  beats 
are  the  exception  among  the  Chelonia.  In  every  one  that  I  worked 
with,  however,  there  were  absolutely  no  spontaneous  beats  for  an  hour 
or  more;  and  I  am  inclined  to  believe  that  where  proper  precautions 
are  taken  to  keep  the  nerve  irritable  and  conductive  there  is  no  escape 
whatever  from  inhibition.  In  one  case  I  observed  a  heart  for  an  hour 
and  a  half,  during  which  time  there  was  not  the  slightest  sign  of  a 
spontaneous  beat.  From  the  fact  that  I  have  not  failed  in  a  single  case 
to  prevent  escape  in  these  animals,  I  am  inclined  to  think  that,  if  the 
experiment  be  properly  conducted,  it  does  not  occur;  at  any  rate  it 
must  be  excessively  late  in  making  its  appearance^. 

Certainly  it  is  among  warm-blooded  animals  that  the  phenomenon 
is  best  developed,  and  it  is  especially  as  it  occurs  in  the  dog  and  cat 
that  it  will  be  studied  in  this  paper.  As  the  technique  of  experiment 
was  about  the  same  in  all  cases,  this  may  be  described  here.  The 
animal  was  tracheotomized  in  order  the  more  easily  to  regulate  the 
anaesthesia.  The  anaesthetic  varied.  Dogs  usually  received  a  sub- 
cutaneous injection  of  1/10  gr.  morphia  over  an  hour  before  the 
experiment ;  this  was  followed  by  a  little  ether  during  the  operation. 
Control  experiments  were  made  with  ether  alone  ;  in  some  the  morphia 
alone  seemed  sufficient  and  no  ether  was  used,  the  results  being,  so  far 
as  I  could  discover,  the  same  whether  one  or  another  of  these 
anaesthetics  was  employed. 

With  cats,  ether  alone  was  generally  employed ;  the  only  objection 
to  its  use  lies  in  the  difficulty  of  controlling  the  amount  given ;  other 
drugs,  especially  chloral  and  paraldehyde,  which  were  tried  as 
substitutes,  proved  unsatisfactory. 

The  use  of  curari  was  avoided,  partly  because  of  the  danger  of 
affecting  the  inhibitory  apparatus  by  an  overdose,  and  partly  because  it 

^  The  above  was  written  before  I  was  aware  of  T.  Wesley  Mills's  work  on  the  same 
subject  (see  this  Journal,  vi.  255.  1885).  Eeference  to  his  paper  will  show  that  my  work 
is  a  repetition  and  confirmation  of  his.  It  is  interesting  to  note  that  by  stimulation  of 
one  vagus  he  held  the  heart  of  a  terrapin  in  diastole  for  four  hours  and  a  half, 


174  T.   HOUGH. 

is  impossible  to  control  the  anaesthesia  after  the  drug  has  taken  effect. 
It  is  important  to  know  the  condition  of  the  animal  in  this  respect, 
for  it  is  clear  that  the  danger  of  producing  a  hyperexcitable  central 
nervous  system,  especially  a  hyperexcitable  vaso-motor  centre,  should  be 
avoided  as  far  as  possible ;  otherwise  the  blood-pressure  tracing  cannot 
be  relied  u})on  to  give  us  accurate  information  of  events  taking  place  in 
the  heart  itself;  and  this  can  be  avoided  only  by  the  proper  use  of 
anaesthetics.  I  have  always  found  that  during  partial  consciousness 
escape,  especially  of  blood-pressure,  is  very  rapid.  The  long  periods 
of  very  low  blood-pressure  in  the  medulla  resulting  from  the  slowing 
or  total  arrest  of  the  heart-beat  we  know  cause  dyspnoea,  with  its 
concomitant  vaso-motor  changes ;  and  it  is  necessary  to  eliminate  this 
factor  as  fai'  as  possible  not  only  by  guarding  against  hyperexcitability 
in  the  medulla  but  even  by  lowering  its  irritability  below  the  normal. 

The  blood-pressure  tracing,  taken  in  the  usual  way  by  means  of  a 
mercury  manometer  and  a  Lud wig's  kymograph,  was  relied  upon  for 
the  graphic  record.  It  should  perhaps  be  mentioned  that  a  27% 
solution  of  magnesium  sulphate  was  iised  in  the  pressure  bottle. 

Usually  both  vagi  were  cut ;  sometimes  only  one ;  the  former 
method  is  preferable  for  the  study  of  escape  since  the  curve  is  not 
influenced  by  inhibitory  impulses  passing  down  the  other  nerve ;  this  is 
of  importance,  for  instance,  when  one  wishes  to  compare  the  curves  of 
escape  when  different  strengths  of  stimulation  are  used.  The  nerve 
was  stimulated  from  a  Du  Bois  Reymond  coil,  which  usually  had  a 
large  bichromate  cell  in  the  primary  circuit.  In  the  first  fifty-four 
experiments  shielded  electrodes  were  used ;  the  nerve  therefore  lay  on 
two  platinum  wires ;  the  results  obtained,  however,  were  unsatisfactory  and 
gave  much  trouble  from  the  impossibility  of  obtaining  uniform  contact 
of  the  nerve  with  the  platinum ;  the  presence  of  a  greater  or  less 
amount  of  normal  salt  around  the  nerve  would  sometimes  escape 
detection  and  short-circuit  a  part  or  in  some  cases  practically  all  ihe 
current  from  the  nerve.  Moreover,  as  suggested  by  Gotch  and 
Horsley',  a  nerve  should  always  be  stimulated  by  placing  the 
electrodes  on  opposite  sides,  so  that  the  current  must  go  transversely 
through  it.  In  accordance  with  this  suggestion  I  had  made  for  this 
purpose  a  special  pair  of  electrodes.  They  consist  essentially  of  a 
vulcanite  bed,  one  end  of  which  can  be  made  fast  in  the  clamp  of  a 
universal  holder,  and  so  the  whole  electrode  may  be  placed   in  any 

1  "The  Mammalian  Nerroas  System,"  Phil.  Trans,  of  Royal  Soc.  of  London,  Vol. 
182  B.  1891,  p.  301. 


ESCAPE  FROM   VAGUS  INHIBITION.  175 

desired  position ;  a  second  piece  of  vulcanite  works  by  a  hinge  joint 
upon  the  first,  a  light  spring  holding  it  down,  so  that  the  nerve,  which 
lies  between  them,  is  in  good  contact  with  both  beds  but  is  not  injured 
by  crushing;  a  platinum  wire  is  placed  on  one  side  of  the  upper  surface 
of  the  lower  bed,  and  a  second  on  the  opposite  side  of  the  under  surface 
of  the  upper  bed ;  these  wires  are  the  electrodes  and  the  nerve  is 
between  them ;  any  current  must  go  through  the  nerve  from  one  side 
to  the  other  and  so  affect  every  fibre  of  it  equally.  The  distance 
between  the  two  electrodes  is  about  six  millimetres.  It  is  much  easier 
to  keep  these  hinged  electrodes  free  from  too  much  moisture  than  the 
ordinary  shielded  ones,  and  one  is  able  to  judge  fairly  accurately  from 
the  position  of  the  secondary  coil  the  comparative  strength  of  stimulation, 
knowiog  that  the  contact  of  the  nerve  with  the  platinum  is  about  the 
same  in  all  cases. 

The  nerve  was  kept  moist  with  normal  salt  solution,  in  which  it  lay 
except  during  stimulation.  Usually  the  animal  was  placed  in  a  warm 
chamber  after  the  completion  of  the  operation ;  the  temperature  of  this 
varied  from  20"  to  25"  C. 

The  chief  points  which  required  attention  during  the  experiment 
were  the  anaesthesia,  which  was  kept  as  far  as  possible  just  at  the  point 
of  disappearance  of  the  lid  reflex,  and  the  proper  contact  of  the  nerve 
with  the  electrode,  including  the  prevention  of  any  change  of  position 
on  the  same. 

With  these  remarks  on  general  technique  the  curves  of  escape  as 
seen  in  dogs,  rabbits,  and  cats  may  be  now  described.  It  has  already 
been  said  that  it  is  very  difficult  to  cause  stand-still  in  the  heart  of  a 
healthy  cat,  and  associated  with  this  is  the  rapid  and  extensive  escape 
from  the  initial  degree  of  inhibition.  In  the  dog  and  rabbit,  on  the 
other  hand,  strengths  of  current  which  are  at  first  able  to  produce 
stand-still  permit  of  only  a  partial  recovery  of  blood-pressure  and  of  a 
still  less  complete  recovery  of  rate;  A.  B.  Meyer  records  the  case  of  a 
dog  where  pulse  was  kept  for  one  hour  at  the  very  low  rate  of  sixty 
beats  per  minute  by  continued  stimulation  of  both  vagi ;  such  a  thing 
is  not  exceptional  in  narcotized  dogs;  on  the  contrary  it  is  the  rule. 
The  heart  of  a  cat  whose  vagi  are  subjected  to  the  same  strength  of 
stimulation  would  certainly  escape  in  that  time  to  a  much  higher  rate. 
The  difference  between  the  two  animals,  however,  is  one  of  degree  and 
not  of  kind ;  the  curves  of  escape  in  the  two  cases  are  essentially  the 
same,  that  of  the  cat  passing  through  its  phases  more  rapidly  than  that 
of  the  dog. 


176  T.   HOUGH. 

When  the  vagus  of  the  dog  is  stimulated  with  a  sufficiently  strong 
current  to  produce  stand-still,  escape  takes  place  sooner  or  later.  This 
is  usually  described  as  being  ushered  in  by  beats  of  regularly  increasing 
frequency ;  and  at  times  this  does  occur,  especially  with  impulses  which 
are  just  strong  enough  to  stop  the  heart ;  it  is  not,  however,  an  accurate 
account  of  what  usually  happens.  The  more  usual  curve  is  where 
there  are  at  first  a  few  beats,  quite  far  apart,  and  the  interval  of  time 
separating  them  may  be  diminished  with  each  new  pulsation  or  not ; 
sometimes  the  tracing  is  quite  irregular  in  this  respect.  Take,  for 
instance,  the  following : 

Exp.  57.  Tracing  8.  11.17.20—11.17.30  a.m.  The  heart  gave  twenty- 
nine  beats  and  the  blood-pressure  was  144  mm.  of  mercury  ;  both  vagi  cut. 

11.17.30  Right  vagus  .stimulated  with  secondary  coil  at  11cm.;  heart 
stops  for  87|^  sec. ;  then  escapes  as  follows — the  time  in  seconds  is  given  for 
each  successive  heart-beat : 

25i,    7,  16i,  21,  21,  15,  5^,  12^,  4. 

It  may  be  said  that  this  irregularity  is  caused  by  the  very  long 
initial  stand-still  and  the  profound  nutritional  changes  introduced  into 
the  heart  thereby.  I  do  not  know  but  that  this  is  true ;  in  point  of 
fact,  the  above  figures  are  from  the  last  tracing  of  a  rather  long 
experiment;  at  the  same  time  similar  results  are  obtained  when  there 
are  not  such  long  initial  stand-stills  and  from  the  earlier  tracings  of  an 
experiment ;  thus  in  experiment  56,  tracing  2,  with  both  vagi  cut,  a 
pulse  of  28  beats  in  ten  seconds,  and  a  blood-pressure  of  135  mm.  of 
mercury,  the  right  nerve  was  stimulated  with  the  secondary  coil  at 
12  cm.;  during  the  first  4i  seconds  of  the  fall  of  the  blood-pressure 
curve  the  heart  gave  two  beats ;  then  followed :  none  for  21  seconds, 
then  at  intervals  of  10|^"  one  ;  11^"  one ;  14|"  one  ;  10"  one  beat. 

Whatever  be  its  explanation,  this  result  is  seen  in  perhaps  half  the 
cases  of  escape  from  complete  stand-still. 

Examples  of  more  regular  escape  are  : — 

Exp.  10.  Tracing  1.  Both  vagi  cut;  left  stimulated  with  secondary  coil 
at  7  cm.  ;  a  stand-still  of  40  seconds,  then  beats  at  intervals  of  18,  13  and 
4  seconds. 

Exp.  21.  Tracing  5.  Both  vagi  cut.  Left  stimulated.  Then  beats  in 
24,  11,  7,  6,  6,  3  seconds. 

These  regular  or  irregular,  but  always  infrequent  beats  may  be 
conveniently  spoken  of  as  constituting  the  first  period  of  escape.     In 


ESCAPE  FROM   VAGUS  INHIBITION.  177 

most  cases  the  character  of  the  curve  suddenly  changes  to  that  of  the 
second  period  in  which  the  heart  beats  regularly  and  much  more  rapidly. 

Escape  then  may  be  said  to  be  ushered  in  in  one  of  three  ways ; 
(1)  by  the  usual  curve,  showing  the  sudden  change  from  the  first 
to  the  second ;  (2)  b}^  the  curve  in  which  there  is  no  sharp  distinction 
between  the  two  periods ;  (3)  where  the  first  period  is  lacking  alto- 
gethei',  the  heart  passing  directly  from  stand-still  into  the  second  period. 

Whatever  be  the  way  in  which  escape  begins,  in  the  vast  majority 
of  cases  the  blood-pressure  tracing  is  sooner  or  later  a  regular  curve, 
the  rate  of  beat  and  blood-pressure  gradually  increasing  to  a 
certain  point,  after  which  it  remains  approximately  constant. 

In  weakened  hearts,  on  the  other  hand,  after  a  certain  number  of 
such  regular  pulsations  a  beat  seems  to  be  dropped ;  there  then  follows 
a  certain  number  of  regular  beats ;  after  which  another  beat  is  dropped; 
and  this  may  continue  for  a  longer  or  shorter  time ;  usually  it  gives 
place  to  the  regular  curve ;  sometimes  it  continues  throughout  the 
whole  period  of  stimulation. 

Some  time  before  the  end  of  a  long  stand-still  the  low  blood-pressure 
has  influenced  the  vaso-motor  centre,  causing  it  to  send  out  powerful 
constrictor  impulses ;  this  is  seen  in  the  slight  rise  which  usually  occurs 
on  the  tracing  of  stand-still ;  the  vascular  system  is  normally  overfilled 
with  blood  and  the  great  constriction  of  the  arterioles  by  diminishing 
the  capacity  of  the  whole  system  is  able  to  make  itself  felt  in  the 
manometer.  This  probably  explains  why,  when  the  regular  and  com- 
paratively frequent  beats  of  the  second  period  of  escape  begin,  blood- 
pressure  is  a  little  higher  for  from  ten  to  thirty  seconds  than  it  is  for  a 
minute  more  or  less  afterward.  At  the  same  time  the  pulse  also  is 
quicker  than  it  is  subsequently,  although  this  increase  in  rate  is  by  no 
means  so  constant  as  the  ino'ease  in  pressure ;  sometimes  both  are 
absent ;  it  would  seem  that  both  are  the  result  of  dyspnoea  or  other 
secondary  influences  upon  the  heart  on  the  one  hand  and  upon  the 
arterioles  on  the  other. 

After  the  first  ten  or  twenty  seconds  of  the  second  period  of 
escape  blood-pressure  generally  falls  slightly,  and  this  is  sometimes 
accompanied  by  a  fall  in  the  rate,  which  lasts  for  a  variable  length 
of  time ;  then  follows  a  very  gradual  increase  both  of  pressure  and 
of  rate ;  the  latter  does  not,  however,  as  a  usual  thing  increase  very 
greatly ;  soon  its  maximum  is  reached,  and  beyond  this,  though  stimula- 
tion be  continued  for  thirty  minutes  or  even  an  hour,  there  is  very  little 
further  escape ;  not  so  however  with  regard  to  pressure ;  this  usually  is 

PH.  XVIII.  12 


17S  T.  nnrcH. 

found  to  be  increasing  noticeably  long  after  the  late  has  become 
practically  constant ;  but  in  long  observations  it  also  sooner  or  later 
reaches  a  maximum,  which  it  subsequently  maintains. 

No  absolute  figures  can  be  given  for  the  time  consumed  in  these 
periods  of  escape ;  the  widest  possible  variations  are  met  with  in  diffe- 
rent animals,  although  it  seems  to  be  more  or  less  constant  for  the  same 
animal ;  I  have  in  vain  attempted  to  find  whether  the  strength  of  stimu- 
lation affects  it;  but  this  factor  seems  to  play  a  very  unimportant  part. 

The  extent  of  escape  depends  partly  upon  the  strength  of  stimulation; 
the  stronger  stimulus  allowing  of  less  complete  escape  than  the  weaker 
(see  section  6  of  this  paper) ;  but  it  depends  chiefly,  so  far  as  the  factors 
coming  into  play  in  my  experiments  are  concerned,  upon  the  condition 
of  the  heart  as  influenced  by  the  anjesthesia ;  the  more  deeply  the 
animal  is  under  the  influence  of  ether  or  morphia,  the  lower  is  the  level 
of  pulse  and  pressure  reached  ;  this  is  especially  true  of  pressure. 

How  incomplete  anaesthesia  may  aflect  the  blood-pressure  tracing 
through  the  agency  of  the  central  nervous  system  has  already  been 
mentioned ;  and  in  this  way  it  affects  more  or  less  fhe  extent  of  escape; 
the  effect  moreover  is  increased  by  its  direct  action  upon  the  irritability 
of  the  cardiac  musculature ;  we  should  expect  to  find,  whether  the 
central  nervous  system  interferes  or  not,  that  the  deeper  the  anesthesia 
the  less  complete  the  escape,  since  the  heart  is  unable  then,  other  things 
being  equal,  to  beat  so  forcibly  and  rapidly. 

We  have  seen  that  in  the  anaesthetized  dog  escape  both  of  rate  and 
of  blood-pressure  goes  to  a  certain  point  and  little  if  any  beyond  that 
point,  no  matter  how  long  the  stimulation  be  continued.  The  question 
arises  whether  there  is  ever  complete  escape  to  the  original  rate  and 
force  of  beat  ? 

In  the  narcotized  animal  there  certainly  is  not  in  escape  from  stand- 
still or  from  decided  slowing ;  I  have  not  seen  a  single  case  of  it  in  the 
dog,  and  it  is  only  in  the  rarest  instances  that  there  is  even  a  near 
approach  to  it ;  usually  where  the  pulse  is  20 — 30  in  ten  seconds  and 
the  blood-pressure  130 — 140  mm.  of  mercury  before  stimulation,  escape 
from  stand-still  rarely  goes  beyond  12  beats  in  ten  seconds  and  a  blood- 
pressure  of  100  mm.  of  mercury.  7,  8,  and  9  are  the  more  usual  figures 
for  rate,  and  70  to  90  mm.  of  mercury  for  blood-pressure.  Extreme  care 
must  be  taken  to  avoid  poor  contact  of  the  nerve  with  the  electrodes  ; 
the  breathing  movements  of  the  animal  frequently  move  the  nerve  so 
slightly  that  the  change  is  unnoticed  although  the  strength  of  stimula- 
tion is  sufficiently  lessened  to  permit  of  more  or  le.ss  complete  escape. 
I  may  add  that  no  such  cases  occurred  while  usinsf  the  hinffed  electrodes. 


ESCAPE  FROM    VAGUS  INHIBITION. 


179 


In  animals  not  so  deeply  narcotized,  though  by  no  means  conscious,  the 
escape  is  somewhat  more  complete :  indeed  in  these  cases  the  pressure 
sometimes  quite  reaches  the  normal. 

Upon  ceasing  the  stimulation  there  is  an  almost  immediate  increase 
in  rate  and  pressure,  thus  showing  that  the  escape  has  not  been  com- 
plete ;  or  rather  that  the  inhibitory  impulses  during  stimulation  were 
still  effectived 

The  most  important  fact  is  that  after  stand-still  the  heart  escapes 
to  a  practically  constant  level  of  rate  and  pressure,  and  will  continue  at 
this  level  for  a  long  time.  It  would  seem  that  there  are  two  separate 
agents  at  work;  the  inhibitory  impulses  on  the  one  hand  and  the 
physiological  processes  which  result  in  the  production  of  the  heart-beat 
on  the  other;  that  at  first  the  former  get  the  upper  hand;  but  the 
latter  gradually  increase  in  activity,  so  that  they  are  able  to  oppose 
more  and  more  resistance  to  inhibition,  until  at  last  a  point  is  reached 
where  the  two  are  io  equilibrium  ;  that  this  condition  can  continue  inde- 
finitely ;  and  that,  when  the  inhibitory  impulses  cease,  the  other  factor, 
now  unopposed,  is  in  many  cases  able  to  cause  a  supra-normal  rate  and 
force  of  beat  which  lasts  for  a  variable  length  of  time,  but  which  sooner 
or  later  gives  place  to  the  normal  or  even  to  a  sub-normal  pulse. 

The  following  are  the  protocols  of  two  typical  experiments ;  in  the 
first  the  sudden  change  from  the  first  to  the  second  stage  is  shown, 
and  this  is  the  usual  form ;  in  the  second  the  one  stage  passes  gradually 
into  the  other : 


Time 


hrs. 


I 

^XPERIME 

NT    60. 

Tracing  VI. 

sees. 

Fractions 
in  sees. 

Eate 

Pressure 

Remarks 

20 

29 

120 

■ 

30 

0 

5.4.30   R  at  9 

40 

0 

50 

0 
0 

y  58|  sec.    No  beats 

10 

0 

20 

81 

0 

/ 

30 

11 

1 
0 

I    lli  sec.     One  beat 

40 

7 
3 

1 
2 

7  .sec.     One  beat 

50 

9 

8 

63 

10 

7  — 

1 

20 

6  + 

There  may  be  an  exception  to  this  statement ;  it  will  be  described  in  section  4. 

12 2 


180 


'j 

r.    HOUGH. 

Time 

Fractions 

Bate 

Pressure 

Remarks 

hrs. 

min. 

sees. 

in  sees. 

5 

6 

30 
40 
50 

7  — 

7 

7 

5 

7 

10 

8- 
8 

67 

No  tracing  until 

5 

9 

8       ,       80     1 

10 

8       1 

1 

No  tracing  until 

f) 

12 

10 

7+          85 
8- 

No  tracing  until 

5 

13 

40 
50 

7  + 
7 

81 

5.14     Off 

I 

EXPERIMENT  57.     Tracin 

g"-. 

11 

15 

20 
30 
40 
50 

29 
0 
0 
0 

143 

11.15.30  Rat  11 
57.^  sec.     No  l)eats 

11 

ir. 

10 
20 

'h 

0 
0 
0 

30 

21 
8i 

1 

0 

I    11  sec.     One  beat 

40 

U 
6" 

1 

0 

[    7},  sec.     One  beat 

50 

4 
51 

1 

0 

1 

>  9\  sec.  One  beat 
4?,  sec.     One  l)eat 

11 

17 

10 
20 
30 
40 
50 

3 

5 
6 

5  + 

11 

18 

10 
50 

7 

8- 

9- 

71 

11 

19 

9- 

11 

20 

40 
50 

9 
9 

11 

22 

10 
20 

9- 
9- 

11 

23 

40 

50 

9 

103 

1193  50     Off 

ESCAPE  FROM  VAGUS  INHIBITION.  181 

At  times,  however,  the  curve  departs  somewhat  from  this  form,  and 
the  most  important  of  these  variations  may  now  be  mentioned.  The 
rhythm  is  not  always  regular  after  the  beginning  of  the  second  period 
of  escape ;  one  form  of  this  has  already  been  described ;  it  consists  in 
the  dropping  of  a  beat  every  now  and  then ;  otherwise  the  pulsations 
go  on  as  usual.  The  dropping  of  these  beats  is  not  synchronous  with 
the  respiratory  movements. 

A  second  kind  of  irregularity  in  the  curve  of  escape,  or  perhaps  only 
an  exaggerated  form  of  that  just  mentioned,  makes  its  appearance 
frequently  after  the  heart  has  been  subjected  to  several  periods  of  pro- 
longed inhibition  and  escape;  it  is  also  frequently  seen  when  very 
strong  stimulating  currents  are  used ;  it  consists  in  alternating  periods 
of  pulsation  and  stand-still ;  indeed  these  tracings  are  strikingly  similar 
to  those  which  Luciani  found  in  isolated  frogs'  hearts  fed  for  a  long 
time  on  centrifugalized  serum i;  this  may  continue  for  ten  or  more 
minutes,  indeed  through  the  whole  period  of  stimulation;  at  other 
times  it  gives  place  to  the  regular  curve  of  escape,  unbroken  by  periods 
of  stand-still.  Sometimes  instead  of  periods  of  complete  stand-still 
there  are  simply  periods  of  very  great  slowing;  this  form  is  more 
commonly  met  with  in  the  cat. 

It  sometimes  happens,  though  very  rarely  in  the  dog,  that,  instead 
of  maintaining  the  level  of  rate  and  pressure  to  which  escape  has  taken 
place,  blood-pressure  falls  from  this  level — which  may  have  been  kept 
for  several  minutes — as  does  also  the  pulse. 

Stand-still  is  produced  in  the  rabbit  as  easily  as  in  the  dog,  although 
it  does  not  last  so  long;  the  heart  rarely  remains  at  rest  for  thirty 
seconds.  Spontaneous  beats  then  occur,  which  are  at  first  rather  irre- 
gular as  to  rate ;  eventually  a  regular  rhythm  is  established,  though  far 
below  the  normal.  Gamgee  and  Priestley  record  quite  rapid  and 
complete  escapes  in  this  animal. 

My  rabbits  were  under  the  influence  of  chloral,  and  not  chloroform 
or  ether  as  were  theirs ;  at  the  same  time  I  do  not  think  that  this  can 
explain  the  differences  in  the  results.  The  following  is  an  example  of 
the  results  I  have  obtained  and  shows  how  comparatively  slight  were 
the  escapes. 

1  Hermann's  Handb.  d.  Phys.  iv,  1,  363 


182 


T.   HOUGH. 


Exp.  38.     Large  male  rabbit.      1  gr.  chloral  per  anutii. 
Tracincr  II. 


Both  vagi  cut. 


Time 

Fractions 

Bate 

Pressure 

Kama 

hrs. 

niin. 

sees. 

in  sees. 

3 

26 

40 

32 

116 

50 

2 

40 

3.26.50     R  a 

3 

27 

10 
20 
30 
40 
50 

7 
3 

2 
0 
0 
0 
3 
4 
3 

29 
26 
18 
18 
36 
40 
32 

3 

28 

10 
20 
30 
40 

3 

5 
5 
6 
6 

28 
28 
28 
30 
30 

3 

30 

50 

9 

38 

3 

31 

10 

9 
9 

40 
40 

20 

9 

38 

^ 

30 

9 

38 

3 

32 

50 

9 

42 

3 

33 

10 

9 

9 

42 
42 

20 

26 

70 

3.33.20    Oil' 

30 

30 

95 

I  am  inclined  to  look  to  the  character  of  the  electrodes  used  as 
explaining  the  difference  ;  just  how  these  act  I  do  not  know ;  I  only 
know  that  in  using  the  ordinary  catheter  electrodes  such  complete 
escapes  occur  in  dogs  quite  frequently ;  they  are  rare  when  shielded 
electrodes  are  used ;  and  never  occur  with  hinged  electrodes ;  un- 
doubtedly these  last  insure  not  only  perfect  but  constant  contact  with 
the  nerve  such  as  cannot  be  obtained  by  the  use  of  either  of  the  other 
patterns.  In  view  of  these  facts  I  must  regard  such  complete  escapes 
as  due  to  errors  of  experiment. 

In  all  my  tracings  from  this  animal  (eighteen  in  all)  a  certain  level 
of  rate  and  pressure  was  established :  the  above  protocol  is  a  fair 
specimen  of  what  always  occurred.  The  number  of  animals  used  was 
not,  however,  great  enough  to  warrant  more  detailed  statements. 

Incidental  reference  has  frequently  been  made  in  various  parts  of 
this  paper  to  the  great  resistance  of  the  cat's  heart  to  inhibition ;  this 
is  shown  by  the  fact  that  stand-still  as  a  general  thing  is  not  obtained  ; 


ESCAPE  FROM   VAGUS  INHIBITION.  188 

by  the  almost  immediate  commencement  of  escape ;  by  the  greater 
height  to  which  the  pulse  and  pressure  rise  while  stimulation  is  bein<r 
contmued,  and  by  the  rapidity  of  this  rise.  These  statements  seem  to 
hold  for  vigorous  animals;  while  among  those  which  give  signs  of 
diminished  vigour,  such  as  low  blood-pressure,  or  failure  to  stand  the 
operation  properly,  tracings  are  obtained  at  times  which  closely  resemble 
those  of  the  dog;  it  should,  however,  be  added  that  even  under  these 
conditions  escape  is  eventually  more  complete  than  it  is  with  the 
dog. 

In  the  cat  also  as  in  the  dog  we  generally  find  that  when  the  heart 
begins  to  escape  there  is  a  temporary  rise  of  pressure  and  sometimes  of 
rate  which  soon  gives  place  to  a  fall ;  afterwards  a  second  rise  begins, 
which  eventually  reaches  a  level  and  remains  there  for  a  longer  or 
shorter  time.  Thus  far  the  curve  is  almost  exactly  like  that  seen  in  the 
dog  when  the  stimulation  at  first  only  slows  the  heart  to  a  considerable 
extent ;  it  differs  from  such  a  curve  in  that  its  phases  are  passed  through 
more  rapidly;  if,  however,  stimulation  be  continued  for  five  minutes 
or  more,  it  is  almost  always  found  that  a  second  fall  of  blood-pressure 
takes  place;  as  already  remarked,  this  is  occasionally  seen  in  dogs;  it  is 
the  rule  with  cats.  What  takes  place  after  this  fall  varies  in  different 
tracings;  sometimes  the  rate  and  pressure  gradually  fall  until  a  new 
level  is  reached,  and  this  level  is  practically  maintained  during  the 
remainder  of  the  stimulation ;  at  other  times  the  fall  is  succeeded  by  a 
rise ;  then  follows  another  fall,  and  so  alternating  periods  of  rise  and  fall 
may  continue  for  an  indefinite  time ;  such  tracings  of  escape  are  fre- 
quently seen  in  weak  hearts,  and  sometimes  in  strong  ones  if  the  stimu- 
lating current  be  of  considerable  strength.  A  notable  example  of  it  is 
furnished  by  Exp.  44,  tracing  8 ;  the  heart  was  weakened  by  repeated 
previous  inhibitions  and  other  insult,  and  there  was  general  collapse  of 
the  animal;  blood-pressure  was  low  and  all  breathing  movements  had 
ceased  ;  the  animal  was  kept  alive,  of  course,  by  artificial  respiration. 
For  twenty-four  minutes  the  vagus  was  constantly  stimulated,  during 
which  time  there  were  some  sixteen  periods  of  alternating  greater  and 
less  effective  inhibition,  whether  measured  by  blood-pressure  or  by  the 
pulse. 

The  protocol  of  experiment  29,  tracing  III.  may  be  given  as  an 
example  of  escape  in  the  vigorous  cat.  Examples  of  escape  in  weak 
cats  have  already  been  given  in  section  2. 


1S4  T.   H  or  GIL 


Exp.  29. 

The 

heart-beats 

and 

blood 

-pressure  are  given   in 

successive 

10  seconds. 

Heart- beat 

35 

35 

15 

14 

22 

27 

27 

28 

28 

28 

26 

Blood -press. 

178 

178 

120* 

120 

155 

170 

178 

176 

176 

176 

176 

Heart- beat 

26 

24 

23 

23 

26 

25 

24 

24 

24 

25 

23 

Blood-press. 

176 

169 

168 

171 

174 

174 

170 

169 

170 

171 

162 

Heart-beat 

24 

23 

23 

24 

24 

25 

24 

22 

25 

23 

24 

Blood-press. 

164 

164 

164 

164 

170 

170 

168 

162 

166 

163 

162 

Heart-beat 

25 

31 

33 

Blood-press. 

166 

176t 

176 

*  Bat 

0.    On. 

t  Off. 

It  will  be  seen  that  the  heart  escaped  to  27  or  28  beats  in  ten 
seconds  and  held  this  for  about  one  minute,  a  rather  short  time ;  the 
rate  then  fell  to  23  or  25  beats,  aud  remained  there  until  the  cessation 
of  stimulation. 

Finally,  in  cats  with  very  high  blood-pressure  (180 — 200  ram.  Hg) 
escape  is  exceedingly  rapid  and  in  most  cases  complete,  even  though 
stimuli  of  considerable  strength  be  used ;  so  that  it  cannot  be  said  of 
this  animal  that  the  rate  and  pressure  never  reach  the  normal ;  when, 
however,  they  do  go  so  far,  continued  stimulation  will  usually  lower 
them  again,  though  to  no  great  extent.  This  exceptional  resistance  to 
inhibition  is  seen  only  in  the  first  or  second  tracings  of  an  experiment ; 
but  it  is  so  frequently  seen  there  that  it  cannot  be  due  to  errors  of 
experiment.  Its  cause  lies  either  in  the  diminished  activity  of  the  in- 
hibitory mechani.sm  or  in  the  greater  vigour  of  the  heart ;  we  have  no 
reason,  however,  to  think  that  the  inhibitory  apparatus  is  less  active  at 
this  time  than  it  subsequently  is ;  and  in  view  of  the  fact  that  such 
tracings  occur  only  when  the  mechanism  of  the  heart-beat  has  not  been 
interfered  with  at  all,  and,  judging  from  the  kymographic  tracing,  is  in 
good  physiological  condition,  the  cause  almost  certainly  lies  in  the 
second  of  the  above-mentioned  possibilities  rather  than  in  the  first. 

4.    The  Heart  escapes,  no  matter  how  slight  the  initial 

SLOWING. 

The  tendency  to  regard  the  escape  of  the  heart  as  the  result  of  some 
sort  of  exhaustion  of  the  inhibitory  apparatus  resulting  from  its 
functional  activity  has  caused  physiologists  to  think  of  it  as  taking 
place  only  when  the  heart  is  either  brought  to  stand-still  or  is  very 
decidedly  slowed ;  and  I  have  in  vain  looked  for  any  reference  to  the 


ESCAPE  FROM   VAGUS  INHIBITION. 


185 


fact,  which  is  easily  verified,  that  it  occurs  uo  matter  what  the  amount 
of  initial  slowing  may  be ;  that  this  escape  from  very  slight  slowing  is 
also  comparatively  rapid  ;  and  that  in  all  cases  it  is  more  complete  than 
that  from  stand-still.  Indeed  in  all  my  work  I  have  seen  but  one  case 
where  the  heart  did  not  escape  more  or  less. 

The  following  protocols  give  examples  of  such  complete  escape  with 
minimal  stimuli : 


Exp.  32.    Tracing  V.    Cat.  Paraldehyde.    Shielded  electrodes.    Intervals 
of  10  seconds. 

Heart-beat      19       19       20  19       19       17       17       18       19       19       19 

Blood-press.    120     120     122  121     121     121*  116     120     122     122     124 

Heai-t-beat       19        18        19  19 

Blood-press.    123     122t  126  124 


*  Ou.    K  at  12. 

t  Off. 

Exp.  58 

.     Dog.     Hinged  electrodes. 

Heart- beat 

24       24       22       22 

22  -f 

22  +     22  -r 

23-     23     23     23 

Blood-press, 

,    140     140     136*  139     139 

140      140 

140     140 

Heart-beat 

23-       23       23 

Heart-       Blood- 

Heart-       Blood- 

hrs.  min. 

sees,          beat        pressure 

hrs. 

min.  sees. 

beat        pressure 

2     58 

30           23           138 

3 

4     50 

23-           128 

3       0 

20           23 

3 

5 

23-         131t 

30           23           134 

10 

23-         129 

3       2 

23- 

20 

23            129 

10           23           131 

3 

7 

23 

3       3 

40           23-                     i 
50           23-        131         I 

On.    R  at  14. 

10 

t  Off. 

23            137 

A  dozen  similar  examples  might  be  added,  taken  from  as  many 
experiments  both  on  dogs  and  cats.  In  fact  whenever  the  heart  was 
slowed  but  two  or  three  beats  every  ten  seconds  escape  took  place 
nearly  or  quite  to  the  normal,  and  the  rate  and  pressure  thus  reached 
was  maintained  throughout  any  length  of  stimulation. 

The  time  taken  for  the  completion  of  escape  is  very  short,  seldom 
over  one  minute ;  shorter,  in  other  words,  than  when  stronger  stimuli 
are  used  and  great  slowing  or  stand-still  at  first  produced. 


186  T.    HOUGH. 

5.     Rapidity  of  Recovery  by  the  Inhibitory  Mechanism  of  the 
Power  to  produce  Stand-still. 

The  reader  is  probably  familiar  with  the  fact  that  a  very  short  time 
is  required  for  the  recovery  of  inhibitory  power  after  the  cessation  of 
stimulation  ;  if  stimulation  be  stopped  as  soon  as  escape  from  stand-still 
begins,  the  heart  can  be  stopped  again  after  the  lapse  of  ten  or  twenty 
seconds ;  and  often  it  is  found  that  the  duration  of  this  second 
stand-still  is  quite  as  long  as  the  first.     Take  the  following  example  : 

Experiment  10.     Tracing  5. 


Dog 

Shielded  Electrodes 

1. 

Both  nerves  stimulated 

25  sec. 

0  beats 

o 

))                  ?) 

6   „ 

1  beat 

3. 

i>                  ») 

9   „ 

6  beats 

4. 

Off  for  32  .sec. 

."). 

Both  nerves  stimulated 

24  sec. 

0  heats 

6. 

^!                                      M 

«   „ 

1  heat 

7. 

11                                      11 

8   „ 

5  beats 

8. 

Off  for   16  .sec. 

- 

9. 

Both   nerves  stimulated 

20  sec. 

(1  beats 

10. 

11                   11 

6    „ 

1  beat 

11. 

11                          n 

10    „ 

7  beats 

12. 

Off  for   14  sec. 

13. 

Both  nerves  stimulated 

18  sec. 

0  beats 

U. 

<)                  't 

6    „ 

1  beat 

The  duration  of  the  necessary  rest  is  not  equally  brief  in  all  cases, 
but  it  is  doubtful  whether  it  ever  requires  more  than  30 — 40  seconds  to 
insure  complete  recovery. 

If,  instead  of  shutting  off  the  current  as  soon  as  the  heart  begins  to 
beat  spontaneously,  escape  be  allowed  to  take  place  for  fifteen  or  more 
minutes  it  is  found  that  even  here  a  scarcely  longer  time  is  needed  for 
the  restoration  of  complete  inhibitory  efficiency.  Thus  in  experiment 
23,  stimulation  continued  from  2  h.  58  m.  30  sec.  until  3  h.  35  m.  45 
sec.  The  initial  stoppage  was  25  seconds,  and  at  the  end  of  stimulation 
the  rate  established  was  7-8  beats  per  10  seconds  with  a  blood-pressure 
of  105  mm.  Hg.  The  current  was  off  from  3  h.  35  m,  45  sec.  until  3  h. 
37  m.  20  sec,  i.e.  for  1  m.  35  sec. :  on  stimulating  again  with  the  same 
strength  of  current  the  heart  was  stopped  for  43|^  sec,  and  the 
curve  of  escape  was  about  the  same  after  this  short  rest  as  it  had  been 
during  the  first  stimulation. 

This  has  an  obvious  bearing  on  the  question  whether  escape  is  an 


ESCAPE  FROM   VAGUS  INHIBITION.  187 

exhaustion  phenomenon  at  all ;  it  is,  of  course,  possible  that  complete 
recovery  from  exhaustion  may  take  place  in  such  a  short  while,  but  it 
is  against  all  analogy;  and  one  is  led  at  least  to  suspect  that  other 
physiological  processes  are  at  the  bottom  of  it. 

6.     Relation  between  the  Strength  of  Stimulus  and  the  Curve 

OF  Escape. 

The  object  of  this  section  is  to  compare  the  curves  of  escape 
obtained  with  different  strengths  of  stimulation.  It  will  be  convenient 
to  treat  the  subject  under  the  following  heads : 

1.  Relation  of  the  strength  of  stimulation  to  the  duration  of 
stand-still. 

2.  Its  relation  to  the  extent  of  escape,  both  of  rate  and  of  pressure. 

3.  Its  relation  to  the  duration  of  escape ;  i.e.  to  the  time  consumed 
in  reaching  a  constant  level  of  rate  and  of  pressure. 

The  difficulty  of  investigating  any  of  these  problems  must  be  at 
once  apparent;  it  has  been  shown  that  the  weaker  the  heart,  the  more 
effective  is  the  same  strength  of  inhibitory  impulse ;  and  the  conditions 
of  most  of  my  experiments  preclude  the  possibility  of  tbe  heart's  being 
in  the  same  condition  during  any  two  tracings.  It  cannot  be  but  that 
very  prolonged  inhibition,  say  for  ten  or  fifteen  minutes,  with  the  slow 
pulse  and  low  blood-pressure  consequent  thereupon,  profoundly  modifies 
the  physiological  condition  of  the  organ.  The  long-continued  anaesthesia 
also  must  have  its  effect  in  weakening  the  heart ;  and  in  point  of  fact 
it  is  found  that  during  an  experiment  of  two  hours'  duration  the  heart 
is  almost  always  weaker  at  the  end  than  it  is  at  the  beginning. 

But  apart  from  this  uniform  fall  of  cardiac  vitality  and  concomitant 
rise  of  inhibitory  efficiency  there  must  always  be  temporary  variations 
in  the  physiological  condition  of  the  organ ;  changes  in  the  depth  of 
anaesthesia  or  in  the  vascular  and  respiratory  mechanisms  may  at  any 
time  affect  the  force  of  the  beat  or  the  activity  of  the  inhibitory 
mechanism,  and  these  variations  cannot  be  entirely  prevented  even  with 
the  utmost  care  and  skilL  We  must  therefore  think  of  the  curve  of 
inhibitory  efficiency  as  showing,  not  a  gradual  rise,  but  a  rise  which  is 
broken  by  temporary  falls ;  indeed  we  have  already  seen  that  at  times 
it  represents  a  fall ;  and  at  other  times,  no  doubt,  the  mean  of  the  two 
curves  is  met  with ;  i.e.  where  there  are  temporary  rises  and  falls,  but 
on  the  whole  no  decided  change. 

The  difficulty  of  the  experiment  is  the  more  apparent  when  we 


188  T.   HOUGH. 

remember  that  these  changes  of  inhibitory  efficiency  not  only  cannot  be 
avoided,  bnt  cannot  even  be  discovered  except  by  actually  causing 
inhibition  ;  they  depend  upon  two  variable  factors,  of  which  the  said 
efficiency  constitutes  the  algebraic  sum,  so  to  speak,  the  condition  of  the 
mechanism  of  the  cardiac  beat,  and  the  condition  of  the  inhibitory 
mechanism  itself  The  only  ready  means  we  have  of  estimating  the 
former  is  by  the  blood-pressure  curve,  and  this  we  know  depends  both 
on  cardiac  and  extra-cardiac  events :  and  we  have  no  means  whatever 
of  estimating  the  latter.  It  is,  therefore,  to  be  expected  that  the 
experimental  investigation  of  the  problem  proposed  in  this  section  will 
not  always  lead  to  uniform  results;  the  utmost  we  can  hope  for  is  that 
in  a  great  number  of  experiments  the  relation  will  in  some  degree 
become  apparent. 

1.  Relation  of  the  strength  of  stimulus  to  the  duration  of  stand- 
still. Evidence  on  this  point  may  be  gathered  from  almost  all  of  my 
experiments  on  dogs,  since  in  most  of  them  the  heart  was  stopped  with 
stimuli  of  different  strengths.  The  greater  number  of  these  experiments 
were  made,  however,  with  other  objects  in  view  and  thus  certain 
complications  were  introduced.  A  number  of  experiments  were 
therefore  made  in  which  stimulation  was  continued  only  through  the 
stand-still,  and  was  stopped  as  soon  as  the  first  or  second  spontaneous 
beat  had  occurred ;  from  five  to  ten  minutes  elapsed  between  any  two 
tracings,  so  that  proper  time  was  given  for  recovery.  For  the 
convenience  of  the  reader  the  results  of  these  experiments  are  tabulated 
according  to  the  strengths  of  current  employed  : 

Ex  p.   1.       8ecoudary  coil  at  5  6  <S  10 

Heart  stopped  I  34,33,33       44*32 

for  (sees.)     J  '  '      ' 

Exp.  4.       Secondary  coil  at      3       4       5       G  7  9       111214 


Heart  stopped  "I 
for  (sees.)      J 


26     22     22     21     24,  23     12*     24     23     25 


Secondary  coil  at  16     18     19     2U 

Heart  stop])ed  | 
for  (sees.)      / 


25     22     22      0 


Exp.  40.     Secondary  coil  at         3  4  7       9  11               12         12^ 

Heart  stopped  I  ^^  .  g^ 

tor  (sees.)     j            '  ' 

Secondary  coil  at  12.6  12|  13 

Heart  .stopped  1  ^f,  .^g  i  -    i  -j 

tor  (sees.)      J  ' 


ESCAPE  FROM    VAGUS  INHIBITION.  189 

Exp.  43.     Secondary  coil  at       3  4  7  8  9       10        11 

Heart  stopped  I         g^     ^j    g3     g^     99    i04     88     81     73,90 
for  (sees.)     J 

Exp.  58.     Secondary  coil  at       7  10  10|        11 

Heart  stopped  1      ^g   g^         68,82,751,641         79         21 
tor  (sees.)     J  '  »      '       j'       ^ 

Exp.  59,     Secondary  coil  at  6  8  10 

Heart  stopped  I         86i,  81         83^,  9U,  85,  86         73^,100 
for  (sees.)     J  -  -.'       ^'       > 

A  study  of  these  figures  shows  that  with  moderately  strong  currents 
the  duration  of  stand-still  is  practically  independent  of  the  strength  of 
stimulation ;  or  in  general,  when  the  secondary  coil  is  anywhere  from 
11  to  7  cm.  from  the  primary,  the  duration  of  stand-still  is  about  the 
same  for  all  stimuli ;  in  some  experiments  this  is  beautifully  shown, 
notably  in  1,  4,  43,  and  59.  The  differences  here  are  so  slight  that  we 
must  regard  them  as  accidental.  Further  inspection  suggests  that  if 
the  current  be  just  strong  enough  to  stop  the  heart,  stand-still  lasts  for  a 
much  shorter  time  than  with  stronger  currents  ;  this  fact  has  been  noticed 
in  many  experiments  ;  of  those  just  quoted  40  and  58  are  cases  in  point; 
in  each  of  these  the  secondary  coil  was  moved  up  carefully  and  the  point 
accurately  found  at  which  stand-still  was  produced,  in  the  former  case 
at  13  cm.,  in  the  latter  at  11,  and  it  will  be  seen  that  the  duration  of 
stand-still  produced  with  these  stimuli  is  very  brief  compared  with  that 
resulting  from  stronger  stimulation ^ 

It  should  be  remembered  that  in  these  experiments  strong  and 
weak  currents  were  alternated  in  order  so  far  as  possible  to  exclude 
errors  arising  from  variations  in  the  efficiency  of  inhibition.  One  other 
matter  should  be  mentioned;  I  have  already  said  that  it  frequently 
happens  that  the  initial  stand-still  is  shorter  than  those  which  follow. 
In  the  above  table  I  have  marked  these  with  an  asterisk  whenever  they 
happen  to  be  given. 

Certain  of  the  above  experiments  (e.g.  58)  seem  to  indicate  that 
very  strong  stimuli  do  not  stop  the  heart  quite  so  long  as  weaker  ones ; 

1  Professor  Howell,  to  whom  I  am  indebted  for  many  useful  criticisms  upon  this 
paper,  has  suggested  that  the  failure  of  minimal  stand-still  stimuli  to  cause  as  long  arrest 
of  the  heart-beat  as  that  caused  by  stronger  stimuli  may  be  due  to  the  running  down 
of  the  bichromate  batteries  used  in  the  primary  circuit.  This  may  be  true,  as  no  special 
precautions  were  taken  in  these  particular  experiments  to  avoid  such  an  error.  But  the 
same  factor  had  occurred  to  me  in  many  other  portions  of  the  work,  and  I  frequently  used 
the  control  of  sending  the  current  through  the  primary  coil  for  three  or  four  minutes 
before  sending  the  secondary  current  into  the  nerve.  So  far  as  I  could  see  this  did  not 
affect  the  result. 


190  T.   HOUGH. 

if  this  be  true,  it  is  easily  explained  by  supposing  some  injury  to  the 
nerve. 

We  may,  therefore,  conclude  that  minimal  stand-still  stimuli  do  not 
stop  the  heart  so  long  as  stronger  ones;  but  that,  if  the  strength  of 
current  be  slightly  increased,  a  point  is  soon  reached  beyond  which  any 
increase  produces  little  or  no  change  in  the  duration  of  stand-still. 

2.  Relation  of  the  stvemjth  of  current  to  the  extent  of  escape,  both  of 
rate  and  of  pressure.  It  has  already  been  shown  that  escape  of  the 
heart  takes  place  no  matter  what  may  be  the  amount  of  slowing  caused 
at  first;  the  problem  for  investigation  in  this  section,  therefore,  is  the 
extent  of  escape  from  different  amounts  of  initial  inhibition. 

Reference  to  the  results  already  given  will  show  that  where  the 
initial  slowing  amounts  to  only  one  or  two  beats  in  ten  seconds,  escape 
is  almost  or  quite  complete.  If  the  inhibition  be  more  decided,  escape 
is  not  so  complete,  although  it  always  takes  place,  and  it  may  be  stated 
as  a  general  rule  that  the  greater  the  initial  slowing  the  less  rapidly 
will  the  heart  beat  when  its  final  level  of  escape  is  established.  Thus, 
in  experiment  56,  tracing  I,  the  following  result  was  obtained. 

Hinged  electrodes.    Intervals  of  1 0  sees. 


20     20     20     20     21  +  23     23 
132 

2.5       2.5       2Gt       27  24 

144  143 


Exp.  56. 

Dog. 

Both  vagi 

cut. 

Hit 

Tracing  I. 

Heart-beat 

29 

16       14 

15 

17 

Blood-press. 

132 

107*  104 

103 

97 

Heart-beat 

24 

24       24 

24 

24 

Blood-press. 

144 

*  On.     R  at  13i.  t  Off. 

The  results  of  the  above  tracing  are  plotted  in  fig.  1,  together  with 
the  curve  of  escape  from  stand-still  as  shown  by  the  next  tracing  of  the 
same  experiment ;  it  will  thus  be  seen  at  once  that  in  the  latter  case 
escape  is  much  less  complete. 

Not  only  should  the  effects  of  stimuli  be  compared  one  of  which 
slows  while  the  other  stops  the  heart,  comparisons  should  also  be  made 
between  the  effects  of  two  stimuli,  each  causing  stand-still,  but  one 
stronger  than  the  other ;  will  the  stronger  current  allow  of  more  or  of 
less  complete  escape  than  the  weaker  ?  For  the  present  let  us  confine 
our  attention  to  the  rate.  The  matter  must  be  investigated  by  com- 
paring different  tracings  taken  from  the  same  animal,  different  strengths 
of  stimulation  being  used  in  different  tracings;  it  is  evidently  best, 
moreover,  to  select  two  strengths  of  current  and  to  use  these  alternately  ; 
we  shall  thus  be  able  to  compare  the  effects  of  the  same  stimulus  at 


ESCAPE  FROM   VAGUS  INHIBITION. 


191 


different  times,  and  so  discover  if  there  have  been  any  decided  change 
in  the  sensitiveness  of  the  heart  to  inhibition. 

Beats  per  lOoeconds 


151 

/ 

/ 

^ — 

■'ff 

\    / 

1 

V 

K 

off 

r" 

\,^ 

J 

3 

f 

S 

1 

7 

Rat/Z 


7  M/nutii 

Fig.  1.     Exp.  56,  I.  and  II.    Curves  of  escape.     Ordinates  represent  number  of  heart- 
beats in  10  seconds.    Abscissae  represent  time  in  minutes  from  the  beginning  of  inhibition. 

This,  indeed,  is  the  only  way  in  which  the  question  can  be  investi- 
gated ;  but  it  presents  a  compUcation,  which  must  be  constantly  taken 
into  account  since  it  cannot  be  entirely  avoided.  This  complication 
arises  from  the  long  periods  of  low  blood-pressure  which  such  treatment 
of  the  heart  necessarily  produces ;  one  would  suppose  beforehand,  from 
what  has  been  said  of  the  relation  between  the  condition  of  the  heart 
and  the  efficiency  of  vagus  stimulation,  that,  even  were  the  stimulus 
the  same  in  all  cases,  it  should  be  found  more  effective  with  each  new 
inhibition.  And  this  is  more  or  less  true:  in  two  experiments  where 
the  same  strength  of  current  was  actually  employed  during  all  tracings 
there  was  less  complete  escape  in  the  last  of  the  six  tracings  than  in  the 
first.  Close  inspection  of  these  curves  however  shows  that  the  increase 
of  efficiency  as  measured  by  the  extent  of  escape  is  not  uniform  ;  that 
in  the  first  tracing,  before  anything  had  been  done  to  the  heart,  escape 
is  much  more  complete  than  it  is  in  any  subsequent  tracing :  that  for 
three  or  four  tracings  after  the  first  one  there  is  little  variation  in  the 
effect  produced ;  the  heart  seems  to  withstand  the  insults  offered  to  it 


192 


T.   HOUGH. 


for  this  length  of  time ;  and  it  is  only  afterward  that  the  effects  of 
exhaustion  make  themselves  felt.  If  six  tracings  be  taken,  for  instance, 
the  sixth  and  frequently  the  fifth  will  show  much  less  complete  escape 
than  the  second,  third,  and  fourth.  In  these  experiments  stimulation 
continued  for  ten  minutes,  more  or  less,  a  rest  of  ten  or  more  minutes 
was  then  given  before  the  next  tracing  was  taken. 

The  results  of  these  two  experiments  only  confirm  what  appears  to 
a  greater  or  less  degree  in  all  my  work  on  the  question  under  discussion 
in  this  section  of  my  paper ;  and  I  think  the  conclusion  may  be  safely 
drawn,  that,  if  in  a  great  number  of  experiments  we  compare  the  second, 
third,  fourth,  and  sometimes  the  fifth  tracings  of  escape  from  stand-still, 
we  may  hope  for  a  satisfactory  answer  to  our  question  ;  at  times  the 
first  will  be  given  also,  and,  if  there  is  no  sign  of  a  weakened  heart,  the 
sixth  and  seventh  may  also  be  taken. 

Thirteen  experiments  upon  this  point  were  made  on  dogs ;  most  of 
them  were  with  the  ordinary  shielded  electrodes,  and  while  their  results 
justify  the  conclusion  drawn  from  those  obtained  with  hinged  electrodes 
T  shall  give  the  results  of  the  latter  experiments  only,  since  these  are 
perfectly  uniform  and  for  obvious  reasons  much  more-  reliable.  The 
following  is  a  tabulated  resume  of  these  results. 

Experiment  55. 


Initial  stand-still 

Rat 

Escaped 

to 

e,  in  beats 

Pressure,  in 

racing 

Stimulation 

in  seconds 

per  10  sees. 

mm.  of  Hg 

III 

Rat     9 

26 

G 

104 

IV 

R  at    7 

37A 

5  + 

91 

V 

R  at  10 

94A 

9  + 

128 

VI 

R  at    5 

34 

Experiment 

56. 

6  + 

59 

II 

Rat  12 

21 

10 

102 

III 

Rat    9 

69 

9 

99 

IV 

Rat  12 

48i 

10 

115 

V 

R  at    9 

87 
Experiment 

57. 

7 

87 

II  a 

R  at  11 

571 

9 

103 

b* 

Rat  10 

88 

6 

76 

III 

R  at    9 

105 

5  + 

70 

Via 

Rat  11 

7 

11 

83 

b 

Rat    9 

43 

8 

VII 

R  at    9 

86 

6  + 

75 

*  Means  that  after  the  heart  has  established  a  rate  of  nine  beats  per  ten  seconds,  the 
current  was  strengthened  by  moving  the  secondary  coil  to  10  cm. 


ESCAPE  FROM   VAGUS  INHIBITION.  193 

Experiment  60, 


I 

Rat    9 

— 

7 

82 

II  a 

Rat  12 

41 

14 

107 

b 

Rat    9 

381 

8  + 

81 

III 

Rat    9 

62 

9 

90 

IV 

R  at  llf 

slowed 

25 

115 

Ya 

Rat  11 

561 

12 

99 

b 

R  at    9 

28i 
Experiment  61. 

7  + 

72 

I 

R  at    9 

50 

2 

30 

II  a 

R  at  12 

28i 

15 

100 

b 

Rat    9 

58^ 





Ilia 

R  at    9 

62 

4 

62 

b 

R  at    7 

slowed 

4 

62 

IV  a 

R  at  11 

61 

16 

102 

b 

R  at    9 

87 

4  + 

48 

For  the  clearer  understanding  of  what  follows  some  of  these  results 
have  been  plotted  in  figs.  2 — 4;  each  figure  contains  two  curves,  one 
showing  the  curve  of  escape  with  the  weaker  stimulus,  the  other  the 
curve  of  escape  with  the  stronger  stimulus.  The  abscissae  represent 
time  in  minutes  from  the  beginning  of  escape,  the  ordinates  the  number 
of  heart-beats  in  ten  seconds ;  the  lighter  lines  give  the  result  of  weaker 
stimulation,  the  heavier  lines  that  of  stronger  stimulation. 
-'  Beyond  showing  that  the  stronger  stimulus  permits  less  complete 
escape,  these  figures  bring  out  another  fact ;  there  is  in  the  escape  with 
stronger  currents  a  tendency  to  irregularity  of  rate ;  a  certain  pulse  is 
reached  but  it  is  not  maintained ;  a  minute  or  more  later  the  heart  is 
found  to  be  beating  more  slowly;  then  it  beats  more  rapidly;  then 
more  slowly,  and  so  on.  This  is  in  marked  contrast  with  what  occurs 
with  the  weaker  stimulus,  that  which  is  just  able  to  cause  stand-still,  for 
instance ;  here  the  heart  steadily  escapes  to  its  level^  of  rate  and  main- 
tains this  level  as  long  as  stimulation  continues.  An  extreme  case  of 
this  irregularity  with  strong  currents  is  where  periods  of  total  inhibition 
alternate  with  a  group  of  beats.  It  is  unnecessary  to  point  out  that 
this  is  exactly  what  occurs  toward  the  end  of  an  experiment  with  almost 
any  strength  of  current  and  has  been  explained  by  the  exhaustion  of 
the  heart.  It  is  a  significant  fact  that  strong  stimuli  can  produce  this 
efifect  long  before  weaker  ones  are  able  to  do  so. 

^  Disregarding  the  first  rise  which  appears  in  many  cases. 
PH.  XVIII.  13 


194 


T.   HOUGH. 


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ESCAPE  FROM   VAGUS  INHIBITION. 


195 


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V 

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<4^ 

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196 


T.  HOUGH. 


In  the  above  discussion  only  the  rate  has  been  taken  into  account ; 
and  under  the  conditions  of  these  experiments  this,  of  course,  is  a  better 
test  of  the  work  of  the  heart  than  is  blood-pressure ;  reference  to  the 
tables  given  on  pages  192-3  will,  however,  show  that  the  level  of  blood- 
pressure  established  in  escape  is  lower  with  the  stronger  stimulus. 

If  in  such  an  experiment  while  the  weaker  stimulus  is  being  used 
the  secondary  coil  be  moved  up  to  the  position  which  gives  the  stronger 
stimulus,  we  obtain  the  result  shown  in  experiments  57,  60,  and  01  of 
the  above  tables ;  the  heart  is  either  brought  to  rest  or  greatly  slowed  ; 
escape  then  takes  place,  but  goes  on  only  as  far  as  the  point  reached  in 
other  tracings  when  this  stronger  stimulus  is  the  one  first  employed; 
the  curve,  in  other  words,  is  the  same  as  when  that  strength  of  stimula- 
tion is  given  to  a  normal  heart  and  not  to  one  already  inhibited.  This 
is  not  true,  however,  when  very  strong  currents  are  used  ;  if,  for  instance, 
the  first  stimulation  be  with  the  stronger  current  (secondary  coil  at  8 — 
9  cm.)  and  after  the  rate  of  escape  is  well  established  the  current  be 
further  strengthened,  it  will  frequently  be  found  that  no  eflfect  whatever 
is  produced;  this  is  almost  what  happened  above  in  experiment  61, 
tracing  8 ;  here  moving  the  secondary  coil  to  7  cm.  caused  a  temporary 
fall,  but  escape  soon  took  place  to  the  original  rate  and  pressure.  An 
example  may  be  added  in  which  no  effect  whatever  was  produced. 

Exp.  56.  Dog.  After  escape  from  stand-still  with  the  secondary  coil  at 
9  cm.,  we  have  : 


Time 


No. 

hrs. 

min. 

sec. 

VII 

2 

2 

50 

2 

4 

20 

2 

7 

20 
30 
40 

2 

8 

20 
30 

Fractions 
in  sees. 

Bate 

Pressure 

7 

58 

7 

75 

7 

76 

7 

76 

7 

79 

7 

72 

7 

74 

Remarks 


R  at  9 


2.7.30    R  at  6 


2.8.30    R  at  0 


The  explanation  of  this  is  evidently  that  the  point  of  maximal 
stimulation  has  been  reached.  This  varies  greatly  with  changing  con- 
ditions ;  generally  in  my  experiments  it  was  when  the  secondary  coil 
was  at  about  8  cm. 

This  is  important  in  showing  that  the  strength  of  stimulation  may 
be  considerably  increased  beyond  the  point  which  causes  stand-still 
before  maximal  effects  are  produced  ;  and  that  the  inability  of  a  stronger 
stimulus  to  cause  longer  stand-still  than  that  caused  by  the  weaker  is 
not  to  be  explained  on  the  assumption  that  we  have  passed  the  point  of 


ESCAPE  FROM   VAGUS  INHIBITION.  197 

maximal  stimulation,  since,  if  the  stronger  stimulus  allows  less  complete 
escape  than  the  weaker,  stronger  impulses  actually  reach  the  heart. 
Indeed  on  the  whole  I  am  inclined  to  think  that  the  stronger  stimulus, 
other  things  being  equal,  stops  the  heart  longer  than  the  weaker ;  but 
that  soon  after  we  pass  the  minimal  stand-still  stimulus  the  differences 
in  the  duration  of  stand-still  are  so  slight  that  they  are  obscured  by  the 
action  of  other  factors. 

3.  Relation  of  the  strength  of  stimulus  to  the  duration  of  escape ;  or, 
to  speak  more  accurately,  to  the  length  of  time  elapsing  before  the  heart 
ceases  to  increase  the  rate  and  force  of  beat  despite  the  continued 
stimulation.  Little  more  can  be  done  than  to  indicate  this  as  a  more 
or  less  probable  way  in  which  a  difference  in  the  strength  of  stimulus 
may  make  itself  felt ;  I  have  made  no  experiments  with  this  point 
specially  in  view,  and  do  not  think  that  the  method  used  of  obtaining  a 
graphic  record  enables  one  to  make  accurate  determinations  of  the  time 
relations. 

This  much,  however,  is  apparent  even  in  my  tracings ;  the  escape 
from  minimal  slowing  never  occupies  more  than  two  minutes  from  the 
beginning  of  stimulation,  while,  if  the  initial  inhibition  be  greater  or 
amount  to  actual  stand-still,  more  time  than  this  is  always  consumed. 

When  we  come  to  compare  the  time  relations  of  two  curves  of  escape, 
each  from  stand-still  but  from  different  strengths  of  stimulation,  we 
find  that  this  is  difficult,  if  not  quite  impossible ;  the  tendency  to  irregu- 
larity of  rhythm  frequently  makes  it  difficult  to  say  at  what  moment 
escape  has  ceased  ;  and  the  differences  in  time  are  so  slight  that  they  are 
generally  obscured  by  secondary  factors ;  we  can  therefore  compare  only 
those  curves  which  show  a  steady  increase  in  rate  and  force  to  the 
escape  level  of  pulse  and  pressure. — Only  this  can  be  said :  if  the  com- 
parison be  made  between  the  results  of  minimal  stand-still  stimulation 
and  stronger  stimulation  it  will  be  found  that  the  former  reaches  the  final 
escape  rate  of  the  latter  sooner  than  the  latter  itself  does.  Thus  in  ex- 
periment 56  we  have : 

Final  Time  required  to 

Bemarks 

This  I'ate  was  reached  in 
II.  (R  at  12)  in  less  than 
2  mins. 

This  rate  was  reached  in 
IV.  (R  at  12)  in  a  little 
over  1  min. 


No.  of 
Tracing 

Stimulus 

Final 
escape  rate 

Time  required  to 
reach  this  rate 

III 

R  at  9 

9 

Over  6  mins. 

Y 

R  at  9 

7 

Over  5  mins. 

198  T.   HOUGH. 

7.    On  Alternate  Stimulation  of  the  Vagi. 

No  study  of  the  escape  of  the  heart  would  be  complete  without 
consideration  of  the  results  of  alternate  stimulation  of  the  vagi.  The 
subject  has  been  studied  by  Tarchanoff  and  by  Gamgee  and  Priestley 
with  more  or  less  conflicting  results.  Tarchanoff*  stated  that  after 
the  heart  of  a  mammal  had  begun  to  escape  from  inhibition  by  one 
nerve  shunting  the  current  into  the  other  is  unable  to  again  cause 
stand-still.  Gamgee  and  Priestley-  repeated  this  work,  and  concluded 
that  "  continued  stimulation  of  one  vagus  never  annulled  or  even  pre- 
judiced the  inhibiting  powers  of  the  other  unless  the  inhibiting  appa- 
ratus had  been  recently  kept  under  stimulation  for  some  time^" 

I  shall  not  attempt  here  to  discuss  the  work  of  those  investigators ; 
my  own  experiments  have  not  been  altogether  satisfactory,  and  I  hope 
at  some  future  time  to  investigate  the  subject.  This  much,  however, 
can  be  said;  both  Tarchanoff  and  Gamgee  are  right  in  what  after  all 
is  the  main  point ;  after  prolonged  stimulation  of  one  nerve  shunting 
the  current  into  the  other  has  no  effect  whatever^;  as  an  example  of 
this  take  exp.  6,  tracing  14. 

1.  L  at  9.     Heart  stops  25  sees. ;  then 

2.  „  „  4     „       1  beat 

3.  ,,  ,,  10     ,,     10  beats 

4.  Nerve  slipped  off  the  electrodes  and  the  heart   beat   normally  for 

21  sec. ;  then 

5.  R  at  9.     Heart  stops  16  sees. ;  then 

6.  „  „  98     „     98  beats 

7.  L  at  9.  „  22     „     22  beats 

8.  R  at  9.  ,,  6     ,,       6  beats 

9.  Stimulation  ceases. 

Similar  results  occurred  over  and  over  again,  so  that  we  may  regard 
it  as  established  that,  during  prolonged  escape  from  the  effects  of 
stimulating  one  vagus,  shunting  the  current  into  the  other  does  not 
change  the  rate  of  beat. 

Summary  of  Results. 

The  experiments  given  in  this  paper  show  that  the  escape  of  the 
heart  from  vagus  inhibition  is  not  the  result  of  the  exhaustion  of  the 

1  Archives  de  Phijsiologie,  Serie  II.  T.  ii.  1875. 

2  This  Journal,  i.  39.   1878.  »  Loc.  cit.,  p.  40. 

•*  Perhaps  it  should  be  added  :  unless  the  two  vagi  have  different  inhibiting  power. 


ESCAPE  FROM   VAGUS  INHIBITION.  199 

inhibitory  fibres  of  the  nerve  either  by  continued  stimulation  or  the 
conduction  of  nervous  impulses ;  that  the  more  vigorously  the  heart  is 
beating  when  the  nerve  is  stimulated,  the  less  efficient  is  inhibition,  and 
vice  versa;  that  the  efficiency  of  inhibition  varies  greatly  in  different 
animals,  there  being  usually  no  escape  in  the  terrapin  while  the  heart 
of  a  cat  can  rarely  be  brought  to  complete  stand-still;  that  in  all 
animals  in  which  the  phenomenon  of  escape  is  well  marked,  the  heart 
escapes  to  a  certain  rate  of  beat  and  maintains  this  rate  so  long  as  the 
same  strength  of  stimulation  is  continued ;  that  this  is  true  not  only 
when  the  initial  inhibition  amounts  to  stand-still,  but  also  when  the 
heart  is  merely  slowed ;  that  the  escape  rate  which  is  finally  established 
depends  upon  the  strength  of  stimulation  of  the  vagus  nerve,  the  pulse 
being  quicker  and  blood-pressure  higher  with  weaker  currents  than  with 
strong  ones;  that  in  escape  from  stand-still,  shunting  the  current  into 
the  other  vagus  cannot  bring  the  heart  to  rest  unless  the  inhibitory 
power  of  the  two  nerves  be  different ;  and  that  one  or  two  minutes,  at 
most,  after  a  prolonged  (say,  ten  minutes)  period  of  inhibition  the  same 
current  will  produce  practically  the  same  curve  of  inhibition  as  before, 
the  stand-still  being  as  long  and  the  escape  neither  more  rapid  nor  more 
complete.  It  is  also  an  interesting  fact  that  after  we  go  beyond  the 
minimal  stand-still  stimulus,  the  duration  of  stand-still  seems  to  be 
independent  of  the  strength  of  stimulation  although  the  subsequent 
curve  of  escape  shows  that  we  are  by  no  means  dealing  with  maximal 
currents. 

Concluding  Remm^ks.  The  rapidity  of  recovery  by  the  inhibitory 
mechanism  of  the  power  to  produce  stand-still,  the  effects  of  alternate 
stimulation  of  the  vagi,  the  peculiar  characters  of  the  curve  of  escape — 
especially  the  establishment  of  a  certain  escape  level  of  force  and  rate  of 
beat — the  relations  of  this  curve  to  strength  of  stimulus  employed,  all 
suggest,  at  least,  that  something  else  than  fatigue  of  the  inhibitory 
apparatus  is  the  cause  of  escape. 

On  the  other  hand,  the  fact  that  inhibition  is  more  effective  in  weak 
hearts  than  in  strong  ones  enforces  the  conception  that  inhibition  is  a 
resistance  of  some  sort  to  the  execution  of  the  events  of  the  heart-beat ; 
a  resistance,  in  other  words,  to  the  activity  of  a  powerful  automatic 
mechanism,  and  this  suggests  at  once  the  familiar  conception  of  resist- 
ance in  the  physiology  of  the  respiratory  centre. 

I  am  strongly  inclined  to  think  that  we  must  seek  here  the  explana- 
tion of  the  phenomena  of  escape,  and  shall  close  this  paper  with  a  brief 
statement    of    the    view   I   am   inclined   to   hold   with   regard   to   it. 


200  T.   HOUGH. 

Inhibition  is  a  resistance  to  tlie  occurrence  of  those  katabolic  changes 
which  yield  the  energy  for  the  heart-beat.  Let  us  suppose  that  these 
changes  are  carried  out  in  such  a  way  that  when  resistance  is  opposed 
to  them  they  can  "  gather  head  "  against  it  and  ultimately  overleap  it. 
This  idea,  of  course,  is  not  new  to  the  literature  of  the  physiology  of  the 
heart-beat\  On  opposing  a  slight  amount  of  inhibitory  resistance, 
therefore,  we  should  slow  the  beat,  since  between  any  two  contractions 
time  would  be  consumed  in  "  gathering  head  "  against  resistance  and  so 
the  diastole  lengthened.  Stand-still  would  thus  be  caused  by  resistance 
of  such  amount  that  considerable  time  must  elapse  before  the  beat  can 
be  produced  against  it;  the  heart  of  a  cold-blooded  animal  shows  the 
phenomenon  of  escape  but  slightly  if  at  all  because  the  automatic 
mechanism  of  the  beat  is  not  so  powerful  and  hence  is  unable  to  over- 
come inhibitory  resistance.  The  final  "  escape  level "  would  be  the 
establishment  of  equilibrium  between  the  katabolic  changes  of  the  beat 
on  the  one  hand  and  the  resistance  on  the  other;  the  greater  the 
resistance  the  slower  must  be  the  final  rate  established.  Finally,  the 
gradual  increase  in  the  rate  and  force  of  beat  to  the  escape  level  is  an 
expression  of  the  "staircase  phenomenon";  Avhen  the-heart  has  once 
overcome  the  resistance  and  given  one  contraction,  the  giving  of  that 
contraction  makes  the  next  one  an  easier  matter  against  the  same 
resistance,  so  that  it  comes  sooner  than  the  first ;  the  third  similarly 
comes  sooner  than  the  second,  and  so  on  until  everything  has  adjusted 
itself  to  the  changed  conditions  produced  by  the  presence  of  the  factor 
of  inhibitory  resistance. 

1  Cf.  Howell  and  Cooke,  This  Journal,  xiv.  198—220.   1893. 


YITA. 


The  writer  of  this  paper  was  born  in  Fort  Royal,  Warren 
County,  Virginia,  June  19,  1865.  He  received  his  elementary 
education  in  elementary  and  high  schools  of  Virginia  and  Mary- 
land, matriculating  at  the  Johns  Hopkins  University  in  the 
summer  of  1883.  He  received  from  the  same  University  the 
degree  of  A.B.  in  June,  1886,  after  which  he  spent  three  years 
as  an  instructor  in  McDonogh  School,  Baltimore  County,  Mary- 
land. Returning  to  the  Johns  Hopkins  University  in  the 
autumn  of  1889,  he  pursued  for  four  years  graduate  studies  in 
Biology ;  he  was  Junior  Assistant  in  Physiology  and  Histology, 
1890-92 ;  and  Fellow  in  Biology,  1892-93.  His  major  subject 
for  the  degree  of  Doctor  of  Philosophy  was  Animal  Physiology, 
and  his  minors  were  Animal  Morphology  and  Chemistry. 


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